Endocrine System: General Principles in Endocrinology (Gloria Marie M.

Valerio, MD) Endocrine System Hormones Circulation Slower/Diffused Nervous System Nerve impulses Faster/Localized

On the other hand, epinephrine is not an example of this because it is synthesized by adrenal medulla but it is not synthesized in the sympathetic nerve endings. The formation of epinephrine from norepinephrine takes place only in the adrenal medulla because the enzyme that will catalyze this reaction is present only in the adrenal medulla that is why there is no conversion of epinephrine from norepinephrine int the sympathetic post ganglionic nerve endings. So epinephrine is a hormone. 3. Neuroendocrine Hormones

Regulate body processes In the body there are two systems that regulate the different body functions or processes and these are the endocrine system and nervous system. These two systems aside from regulating different body processes or functions can also provide a means of communication among the different cells of the body. Meaning to say, they enable signals from one cell to be transmitted to another cell causing that cell to respond. The endocrine system can regulate body functions or processes by releasing chemical substances called hormones into the different body fluids and when we say body fluids we mean circulating blood and interstitial fluid. So from the body fluids, hormones are transported to a specific site where they act on specific target cell eliciting a physiologic response from the target cell. Regulation of the different body processes by the endocrine system is said to be slower but more diffuse. Slower, meaning the latent period or the interval between hormoneal stimulation and target cell response is longer. Diffuse because there are some hormones that can act on several target cells at the same time. On the other hand, the nervous system regulates body functions or processes by generating action potentials or nerve impulses and these action potentials or nerve impulses are transmitted by specific efferent or motor neuron to specific target cell or effector cell again eliciting a physiologic response from the target cell. And transmission of impulses from a motor neuron to an effector or target cell is also mediated by a chemical substance this time we have a neurotransmitter agent. Now regulation of body processes by the nervous system is faster. Faster meaning the latent period between nervous stimulation and target cell response is shorter. Localized because remember that specific motor neuron will innervate only specific effector cell. These are the two systems that regulate the different body functions or processes and one thing common to both system is their actions are mediated by chemical substances; hormones for the endocrine system, neurotransmitter agent for the nervous system. Types of Chemical Messenger System (Mediators) 1. Neurotransmitters These are chemical substances synthesized by neuroendocrine cells but released into the blood and NOT in the synaptic cleft. There are two hormones synthesized by hypothalamic nuclei, stored and released by the posterior pituitary gland into the circulating blood and these are oxytocin and the antidiuretic hormone (ADH). 4. Paracrine

Paracrines are also hormones. It is synthesized by an endocrine gland but released only into the interstitial fluid and NOT in the circulating blood. The target cell is located near the secretory cell. We will talk more about the paracrine control system when we go to the actions of insulin and glucagon. 5. Autocrine

These are also chemical substances released into the interstitial fluid. They act on the same cell that will synthesize them. Example is tumor growth factor (TGF). Tumour cells secrete a growth factor into the interstitial fluid and this growth factor will act on the same tumour cell stimulating growth of the tumour cell. 6. Cytokines

These are peptides synthesized and released by the cells of the immune system and their main function is to mediate the actions of the cells of the immune system. Different Body Functions or Processes Regulated by the Endocrine System 1. Chemical Homeostasis Protein metabolism Carbohydrate metabolism Fat metabolism Water and electrolyte metabolism

Examples are acetylcholine and norepinephrine. How would you classify a chemical substance as a neurotransmitter agent? First, it has to be synthesized in the axon terminal of a neuron. Next, its release is due to an action potential or nerve impulse reaching the axon terminal. The release of the NTA is by exocytosis into the synaptic cleft and exocytosis is facilitated by calcium ions. 2. Endocrine Hormones

Under this, we have regulation of carbohydrate, fat and protein metabolism. To give you examples of hormones that regulate carbohydrate, fat and protein metabolism, we have insulin and glucagon from the pancreatic islets of Langerhans; growth hormone from the anterior pituitary gland; even thyroid hormones from the thyroid gland; cortisol from the adrenal cortex; epinephrine and norepinephrine from the adrenal medulla. Next, still under chemical homeostasis is regulation of water and electrolyte metabolism. Hormones involved are ADH from the posterior pituitary gland, parathyroid hormone (PTH) from the parathyroid gland and aldosterone from the adrenal cortex. 2. Reproduction

This is also a chemical substance this time synthesized by endocrine glands. Upon stimulation, they are released into the body fluids mostly into the circulating blood and an endocrine hormone will act on a target cell that is located far from the secretory cell. That is why it circulates first because the target cell is far from the secretory cell. Can a hormone be a neurotransmitter agent or a neurotransmitter agent be a hormone? Yes, example is norepinephrine. Remember that norepinephrine is synthesized by sympathetic post ganglionic nerve endings and at the same time it is also synthesized by a gland which is the adrenal medulla. 1 Shannen Kaye B. Apolinario, RMT

Reproduction is completely dependent on the endocrine system and this will involve the actions of sex hormones like estrogen and progesterone from the ovaries, testosterone from the testes. 3. Growth

In relation to growth, the endocrine system can stimulate cellular growth, division, differentiation as well as metabolism. Examples

of hormones that stimulate growth are growth hormone from the anterior pituitary gland and thyroid hormones from the thyroid gland. Even insulin, estrogen, progesterone, testosterone can all stimulate cellular growth. 4. Behavior

3.

Thyroid Gland T3, T4, Calcitonin

There are two types of secretory cells in the thyroid gland. First, we have the follicular cells that secrete the thyroid hormones T3 and T4. These thyroid hormones can act on almost all cells of the body. Then we have the parafollicular cells that secrete calcitonin and the major target organ of calcitonin is the bone. 4. Parathyroid Gland - PTH

There are some behavioural patterns that can also be influenced by specific hormones. For example, in patients under prolonged corticosteroid therapy, this may induce on the patient a manic depressive type of behaviour. In times of stress, you are able to cope with stressful condition because the adrenal medulla is stimulated to increase the secretion of epinephrine and norepinephrine. Even cortisol, it is also considered an anti-stress hormone. The endocrine system has three major components. First, we have a group of secretory cells or what we call endocrine glands. When stimulate, they will release a chemical substance into the body fluids mainly into the circulating blood and that is a hormone. This hormone will be transported to a specific site where it will act on specific target cells. These are the components of the endocrine system and we will now discuss each component. Classification of Endocrine Glands I. Purely Endocrine

Parathyroid glands secrete the parathyroid hormone. Target organs of PTH are the bone, intesinte, kidneys. 5. Islets of Langerhans Insulin, Glucagon

Among the hormones secreted by the pancreatic islets are insulin and glucagon. The target cells of insulin are muscle cell, adipose cell and liver cell. For glucagon, it has only one target organ and that is the liver. 6. Adrenal Cortex MC, GC, Androgen

In the body, endocrine glands are grouped into two. First, we have what we call purely endocrine glands. Purely endocrine because their only function is endocrine and that is to secrete hormones. 1. Anterior Pituitary Gland (Adenohypophysis) GH, PrL, TSH, ACTH, FSH, LH

The adrenal cortex is divided into three layers, each layer secreting a different type of hormone. The outermost layer is the zona glomerulosa that secretes mineralocorticoids. The most predominant of the mineralocorticoids is aldosterone. The middle layer is the zona fasciculata that secretes glucocorticoids as well as androgens (more of glucocorticoids that androgens). The most predominant of the glucocorticoids is cortisol. The innermost layer is the zona reticularis that also secretes glucocorticoids and androgens but this time more of androgens than glucocorticoids. The target cells of aldosterone are the DCT, collecting ducts of the nephron. As for cortisol, just like T3 and T4, it can act on almost all cells of the body specially the cells of the immune system. When we say androgenic hormones, these are hormones with masculinising effects. 7. Adrenal Medulla EP, NEP

Among the hormones secreted by the anterior pituitary gland are growth hormone (GH) or somatotropin or somatotrophic hormone, prolactin (PrL) or lactotrophic hormone, thyroid stimulating hormone (TSH) or thyrotropin, adrenocorticotropic hormone (ACTH) or corticotrophin, two types of gonadotrophic hormones or gonatropins: follicle stimulating hormone (FSH), luteinizing hormone (LH). The target cells or organs of each hormone: Growth hormone - among its many target organs are the liver, bone, muscle soft tissue. Prolactin mammary gland Thyrotropin thyroid gland Corticotrophin adrenal cortex FSH and LH ovaries in females, testis in males

Adrenal medulla secretes catecholamines epinephrine and norepinephrine. These catecholamines can also act on almost all cells of the body. 8. Ovaries Estrogen, Progesterone

In females, ovaries secrete estrogen and progesterone. These two hormones regulate the female reproductive function. Its target organ is the female reproductive organs 9. Testes Testosterone

Take note that these hormones are called trophic hormones. Trophic, meaning to say, they can stimulate growth as well as secretory activity of their respective target glands or target organs. If you notice, these trophic hormones can actually regulate the functions of almost all the other endocrine glands in the body so that when we say master gland, we refer to the anterior pituitary gland. 2. Posterior Pituitary Gland (Neurohypophysis) Oxytocin - ADH,

In males, the testes secrete testosterone. Testosterone regulates the male reproductive function and its target organ is the male reproductive organs. Why are the ovaries and testes included as part of purely endocrine glands but it has gametogenic functions? Its gametogenic functions are completely dependent on the hormones. II. Partly Endocrine Aside from secreting hormones, they can serve other functions. 1. Nerve Endings Ach, EP Nerve endings release acetylcholine and norepinephrine. 2. GIT Gastrin, CCK, Secretin

Take note the posterior pituitary gland does NOT synthesize any hormones. Its major function is to store and release hormones that are synthesized by hypothalamic nuclei. Again, there are two hormones synthesized by hypothalamic nuclei, stored and released by the posterior pituitary gland. First is antidiuretic hormone (ADH) or arginine vasopressin. The target cells of ADH are DCT and collecting ducts of the nephron and vascular smooth muscle. The target cells of oxytocin are the muscular layer of the uterus or myometrium and myoepithelial cells of the breasts.

Also considered a partly endocrine organ is the gastrointestinal tract. Remember that the mucosal glands in the GIT can

Shannen Kaye B. Apolinario, RMT

secrete many hormones and the most predominant are gastrin, cholecystokinin and secretin. Gastrin stimulates secretion of hydrochloric acid (HCl) by the parietal cells on the stomach for the conversion of pepsinogen to pepsin, increases gatric motility for increased gastric emptying, stimulates growth of the gastric mucosa, stimulates insulin and glucagon secretion, stimulates contraction of the lower esophageal sphincter. Cholecystokinin (CCK) stimulates the contraction of gallbladder, relaxation of sphincter of Oddi for the release of bile to the duodenum, stimulates secretion of enterokinase, stimulates the pancreas to release digestive enzymes from the acinar cells. Secretin stimulates the pancreatic ductal cells to secrete alkaline fluid rich in bicarbonate. 3. Kidneys Erythropoietin, Vit. D H-H Portal Vessels RH/RF IH/IF

Hypothalamus

Anterior Pituitary

Posterior Pituitary

Physiologically, the pituitary gland is divided into two parts. 80% of the pituitary gland is the anterior pituitary gland or adenohypophyis and the remaining 20% is the posterior pituitary gland or neurohypophyisis. In between, there is the parts intermedia which in human beings is avascualar or no blood supply so it has no function. We also mentioned that the hormones secreted by the anterior pituitary gland can regulate the functions of almost all the other endocrine glands in the body that is why it is called the master gland. But the main activity of the anterior and posterior pituitary gland is regulated by a higher center which is the hypothalamus. There is a network of blood vessels connecting the hypothalamus to the anterior and posterior pituitary glands and we call this the hypothalamic-hypophyseal portal vessels. In addition, the posterior pituitary gland is actually an outgrowth of the hypothalamus so there are nerve tracts that will connect the hypothalamus to the posterior pituitary gland. So the connection is vascular and on the other is vascular and neural. How does the hypothalamus regulate posterior pituitary activity? It is also neural. Nerve impulses can be transmitted by nerve tracts to the posterior pituitary gland and that will stimulate the posterior pituitary gland. Vascular-neural connection, neural regulation. In the anterior pituitary gland, vascular connection. The hypothalamus regulate anterior pituitary activity is through hormonal regulation. The hypothalamus can secrete releasing hormones or releasing factors into the hypothalamic-hypophyseal portal vessels and these releasing hormones will then be transported to the anterior pituitary gland where they will act on specific cells of the anterior pituitary to cause the secretion of specific trophic hormones. Also, the hypothalamus can secrete inhibitory hormones or inhibitory factors this time inhibiting specific cells in the anterior pituitary gland from secreting specific trophic hormones. Vascular connection, hormonal regulation. Hormones Secreted by the Hypothalamus 1. GHRH (Somatotropin Releasing Factor) (+) GH. Growth hormone releasing hormone or somatotropin releasing factor stimulates secretion of growth hormone GHIH (Somatostatin) (-) GH. Growth hormone inhibitory hormone or somatostatin inhibit growth hormone secretion. PIH (-) PrL. Prolactin inhibitory hormone which is said to be the same as dopamine so it will inhibit prolactin secretion. PRH (+) PrL. Prolactin releasing hormone that will stimulate prolactin secretion. TRH (+) TSH, PrL. Thyrotropin releasing hormone can stimulate secretion not only of thyrotropin or TSH but also of prolactin. CRH (+) ACTH, MSH. Corticotropin releasing hormone stimulates the secretion of ACTH or coticotropin. But take note in the anterior pituitary gland, the cells that secrete corticotropin can secrete another substance which is structurally related to corticotropin and that is the melanocyte stimulating hormone. But in human beings, there is more ACTH than MSH. Both of them have a hyperpigmenting action. GnRH (+) FSH, LH. Gonadotropin releasing hormone will stimulate the secretion of the two types of gonadotropins: LH and FSH.

The kidneys secrete two hormones: erythropoietin and the active form of vitamin D. The target organ of erythropoietin is the bone marrow. The target organs of vitamin D are the same as in PTH bone, intestine and kidneys. 4. Placenta - HCG

During pregnancy it is the placenta that secretes the hormones of pregnancy that will include the human chorionic gonadotropin (HCG). 5. Heart ANP

The atrial muscle cells secrete atrial natriuretci peptide. The target cell of ANP is the DCT for natriuresis. Its secretion is stimulated if there is increased in blood volume in the right atrium when there is increased venous return. 6. Skin Melanin

In the skin, we have the melanocytes that secrete melanin for increased skin pigmentation. 7. Liver IGF, VIt. D

One of the hormones or protein mediators secreted by the liver is what we call insulin-like growth factor (IGF) or somatomedin. There are several types however insulin-like growth factor I (IGF I) or somatomedin C mediates the actions of growth hormone related to growth. The liver can also produce several form of vitamin D but they are less active than the one produced by the kidneys. 8. Pineal Gland Melatonin

2. 3. 4. 5.

Pineal gland secretes melatonin. Melatonin is synthesized from serotonin. The synthesis of melatonin follows a cyclic process. It is stimulated by darkness but inhibited by light so that means that melatonin can actually transmit signals that will inform the center that night time has arrived so that the different body processes can be regulated accordingly. Also, melatonin is said to induce sleep, 9. Hypothalamus

6.

Aside from endocrine function, the thirst center, satiety center (main ganglion of autonomics), temperature regulation are all located in the hypothalamus. 7.

Shannen Kaye B. Apolinario, RMT

*** Remember the abbreviations because its name already indicates its action. If it is releasing hormone, it is from the hypothalamus while stimulating or trophic hormones is from the anterior pituitary gland.

bind with receptor. If it is bound to a protein, it cannot bind to the receptor. Protein bound hormones are inactive but it has three uses. Protein binding can prolong plasma half-life a hormone. Protein binding will facilitate the transport of a hormone to the target cell. And it also acts as a reservoir, meaning to say, when the free hormone has already been utilized by the target cell, it can be unbound from protein binding converting it into an active form. The binding proteins are produced by the liver and estrogen can actually stimulate the liver to stimulate the production of binding proteins. In the plasma, an equilibrium exists between proein bound hormone and free hormone. For example, there is excess free hormone, the excess will bind to plasma protein so that will render the hormone inactive and that will prevent overstimulation or over-activity of the target cell. On the other hand, when the active hormone has been used up, the free or active hormone concentration will decrease, protein bound hormones will unbound making it active so that will prevent hypostimulation or hypo-activity of the target cell. 7. Main site of inactivation: liver

Hormones I. General Characteristics 1. Secreted by a specific group of cells

Hormones are chemical substances secreted by specific group of secretory cells or what we call endocrine glands. 2. Thrown directly into circulation and other body fluids

As differentiated from exocrine glands, endocrine glands are ductless so that the hormones or their secretory products are thrown directly into the body fluids mostly into the circulating blood. 3. Do not create additional function in the body

We mentioned that the main function of the endocrine system is to regulate body processes or functions. Take note that they regulate existing body functions or processes. They do not create a new function in the cell, they do not add another function to the cell, they only regulate existing body functions and that is done by acting on the different intracellular metabolic enzymes. Hormones can either increase or decrease the synthesis as well as activity of the different intracellular enzymes and therefore can either increase or decrease the rate of existing chemical processes in the cell. What is the difference between a hormone and an enzyme? Both are chemical substances. Enzymes will catalyze the chemical reaction and the hormone will act on the enzyme. Is renin a hormone, an enzyme or both? According to Dra. Viliran, it is very controversial. It cannot be classified if it is a hormone, an enzyme or both. 4. Onset and duration of action

While there are some hormones that can be inactivated in the target cell, most of the inactivation takes place in the liver. 8. Removal from the circulation

The products of hormone inactivation are cleared from the plasma through the kidneys. II. Classification According to Chemical Composition 1. Polypeptide Hypothalamic hormones Anterior / Posterior pituitary hormones PTH, Calcitonin Insulin, Glucagon

As to onset and duration of action, we already mentioned that in the endocrine or hormonal system, the latent period is longer. However, once the target cell responds to the hormone, the duration of the response is also longer. 5. Plasma concentration

What is the difference between a polypeptide and a protein? Protein is larger because it is made up of several polypeptides. Hypothalamic hormones: releasing hormones and inhibitory hormones from the hypothalamus EXCEPT for dopamine. Anterior pituitary hormones or the trophic hormones but take note there are three anterior pituitary hormones that are not purely proteins instead they are glycoproteins and these are TSH, FSH and LH. Then you have ADH and oxytocin from the posterior pituitary gland, PTH, calcitonin, insulin and glucagon. So these are polypeptide or protein hormones. [Synthesized in the RER] Preprohormone Pro-hormone Active hormone

In the circulating blood, hormones are present in low concentration. In fact you need only a small amount of a hormone to stimulate the target cell. 6. Transport Blood = 2 forms Protein-bound (inactive) Free (active)

Liver binding proteins Estrogen (+) liver inc. production of binding proteins Excess free hormone protein-binding inc. inactive Dec. free hormone protein bound hormones are released

In the circulating blood, hormones are present in two forms, either they are protein bound or free. Protein bound hormone is biologically inactive. It is the free hormone that is biologically active. Protein bound hormones are inactive because it cannot pass through the cell membrane and before a hormone can act on its target cell, it has to 4 Shannen Kaye B. Apolinario, RMT

What are the characteristics or properties of polypeptide or protein hormones? In the secretory cells, they are synthesized in the rough endoplasmic reticulum from a large precursor called a preprohormone. A preprohormone is cleaved to form a smaller molecule which is now called a prohormone. Usually they are not released into the circulating blood and they are inactive. A prohormone will be cleaved to form a smaller molecule which is now the active hormone and this active hormone will be stored temporarily in secretory vesicles released only upon stimulation. So it means that protein hormones can be stored and its secretion is not continuous , only upon stimulation. Secretion is also by exocytosis, facilitated by calcium ion. In the circulating blood, protein or polypeptide hormones are soluble so they are transported mainly in the unbound form and since they are

unbound, its plasma half life is shorter. Also, protein or polypeptide hormones cannot cross the cell membrane and it cannot be given orally (e.g. insulin) because it will be digested by the GI enzymes. 2. Biogenic Amines T3, T4 EP, NEP PIF (Dopamine)

The neurotransmitters released either into the neuromuscular or neuroeffector junction also act locally because remember at the neuromuscular or neuroeffector junction, the axon terminals are close to the membrane of the effector cell. 2. General Hormones Site of effect is distant from site of release Examples: thyroid hormones, growth hormones, trophic hormones from adenohypophysis

Hormones that are synthesized from the amino acid tyrosine are classified as biogenic amines and this will include the thyroid hormones - T3, T4, catecholamines epinephrine and norepinephrine, as well as the prolactin inhibitory factor or dopamine. T3 and T4 are synthesized by the thyroid follicular cells. After synthesis, they are stored temporarily in the lumen of the thyroid follicle bound to a large glycoprotein molecule that is thyroglobulin. Just like the protein or polypeptide hormones, the secretion of T3 and T4 is not continuous. It is only secreted upon stimulation so they can be stored. They are also released by exocytosis into the circulating blood and this time, 99% of circulating thyroid hormones are bound to plasma proteins and only 1% is free. Since many are bound to plasma proteins, its half life is long. Thyroid hormones can cross the cell membrane. The secretory product of adrenal medulla is 80% epinephrine, 20% norepinephrine and a very small amount of dopamine. So this PIF or dopamine is not synthesize in the hypothalamus only, it is also synthesized in the adrenal medulla. In the circulating blood, they are present in two forms, either bound or loosely bound to albumin and they cannot cross the cell membrane. 3. Steroid Estrogen, Progesterone, Testosterone Cortisol, Aldosterone, Androgens Vitamin D

General hormones are hormones that act on target cells that are located far from the secretory cell. They are released in the blood, it has to be transported in a distant site from the secretory cell. Examples are thyroid hormones. From the thyroid gland in the neck, thyroid hormones can act on the heart, they can act on the bone and muscle, it can act on the GIT and all are far from the thyroid gland. Another example is growth hormone from the anterior pituitary gland, it will act on the liver in the abdominal cavity, bone, muscle, all of which are far from the anterior pituitary gland. Also, the trophic hormones from anterior pituitary gland, example is TSH. So from the anterior pituitary gland, it has to be transported in the thyroid gland. ACTH from the anterior pituitary gland, it has to be transported to the adrenal glands. So the target cells are far from the secretory cells. Mechanism of Action of a Hormone 1. Hormone-Receptor Interaction Receptors: o Are chemical agents o Stereospecificity o Number can increase of decrease; can even disappear Up-regulation = increase in one hormone can increase number of receptors Down-regulation

Hormones that are synthesized from cholesterol are classified as steroid hormones and this will include sex hormones, adrenocortical hormones and vitamin D. This time, they are lipid soluble so they are not soluble in the circulating blood. Again, they are present in the circulating blood mostly bound to plasma proteins so its half life is long but they are not stored in the secretory cells so whatever amount that is synthesized are also released. Since they are lipid soluble, they can readily cross the cell membrane. III. Classification According to the Site of Target Cell 1. Local Hormone Site of effect is close to site of release Examples: o Paracrine system of pancreatic islet cells Beta cells (-) alpha cells (insulin) (glucagon) Alpha cells (+) beta cells (glucagon) (insulin) o NTA Ach and NEP

Before a hormone can act on a target cell, it has to bind with receptors in the target cell so you need a hormone-receptor interaction or a hormone-receptor complex. What are receptors? They are chemical subunits most of them are proteins and one important property of these receptors is stereospecificty. It means that the configuration of one receptor can only match to the configuration of one hormone. So the receptor for estrogen cannot bind with progesterone, receptor for T3 cannot bind with PTH, receptor with insuin cannot bind with glucagon so the hormone-receptor interaction is very specific. Since these receptors are proteins, they can be degraded or resynthesized so that their number in the target cell is not constant. It can either increase or decrease or the receptors may disappear from the target cell. Once its number decreased or disappeared, even if there are plenty of hormones there will be no action in the target cell. Example: there are two types of diabetes mellitus 1 and 2. In type 1, there is destruction of the pancreatic cells thus there is really no insulin so that the blood glucose level continues to increase. In type 2, the pancreatic B cells are normal or sometimes insulin secretion is higher than normal but the blood glucose level keeps on getting higher because the receptors either decreased or disappeared on the target cell. Increased estrogen Increased production of receptors Oxytocin In relation to this, we have the principle of up-regulation of receptors. Up-regulation wherein if there is an increase in one hormone, this can up-regulate or increase the number of receptors for itself or for another hormone. For example, if hormone A increased, in up-regulation, it will also increase receptors for itself or for other hormones. Another example is during the last trimester of pregnancy, that is where the secretion of estrogen is highest and one important action of estrogen is to increase the production of receptors for oxytocin in the myometrium of the uterus. So that once the posterior pituitary gland secreted oxytocin, it will now bind with the receptors in the myometrium and it can stimulate uterine contractions. One action of oxytocin is to stimulate uterine contraction but oxytocin per se cannot stimulate uterine contraction

If the target cell is located near the secretory cell, we call the hormone released as a local hormone. Most of the GI hormones are local hormones. Also included is the paracrine control system that exists in the pancreatic islets of Langerhans. So in the pancreatic islets there are different types of secretory cells secreting different types of hormones. What can happen is that insulin secreted by the cells can inhibit cells from secreting glucagon. It is adjacent to one another so insulin can be released in the interstitial fluid and not in the blood. Same thing with glucagon from the cells can stimulate cells to secrete insulin. So they are adjacent to each other and it is only in the interstitial fluid where the hormones are released.

Shannen Kaye B. Apolinario, RMT

unless the uterus has been exposed to a large amount of estrogen so oxytocin can actually stimulate contraction of an estrogen-primed uterus. It is estrogen that will stimulate the production of receptors for oxytocin. Increased progesterone > Increased estrogen Decreased receptor for estrogen On the other hand, sometimes if there are excessive amount of hormone, a large amount will bind to the receptor so the receptor is desensitized or destroyed it is down regulated. Excess hormones can now decrease the receptors in the target cell for itself or for another hormone. Example, during the post-ovulatory phase of the female monthly cycle the predominant hormone secreted is progesterone although you still have estrogen. One action of estrogen is to stimulate the innermost layer of the uterus called endometrium to proliferate. When the concentration of progesterone increases, it down-regulates the receptors for estrogen so receptors for estrogen in the endometrium is decreased so even if you have estrogen, it cannot stimulate endometrial proliferation and the endometrial thickening stops. Hormone-Receptor Interaction Location of Receptors: Cell membrane o Protein o Peptide o Catecholamines Cytoplasm o Steroid Nucleus o T3, T4 There are receptors located in the plasma or cell membrane of the target cell and that is where protein or polypeptide hormones as well as catecholamines bind to. Or in other words, the receptors for protein or polypeptide hormones as well as for catecholamines are located in the cell membrane because remember that they cannot cross the cell membrane. For steroid hormones which are lipid soluble, they can readily cross the cell membrane, bind with intracellular or cytoplasmic receptors. Thyroid hormones on the other hand bind with nuclear receptors. Membrane Receptors 1. Ion channel linked receptors H + receptor open ion channels Ion channel linked receptors or simply known as ligand gated ion channels. For example, acetylcholine when it binds with a nicotinic receptor on the membrane of the skeletal muscle cell, that will open up sodium channels allowing Na influx, depolarizing the membrane, exciting the effector cell. 2. G-protein couple receptor a. 2nd messenger mechanism

activation of G-proteins on the inner surface of the membrane. Activated G-proteins will activate an intracellular enzyme, in this case it is adenylyl cyclise that will lead to the formation of cAMP. cAMP is the intracellular ligand or the 2nd messenger. The first action of cAMP is to activate another intracellular enzyme that is protein kinase that will cause phosphorylation of specific intracellular proteins and this will now lead to stimulation of specific biochemical intracellular reactions. When this happens, this could lead to the opening of ion channels, stimulate gene transcription, formation of intracellular proteins, all of which will change the metabolic set-up of the cell allowing the cell to respond to the presence of a hormone. Hormones that use Adenylyl cyclase cAMP system CRH, GHIH ACTH, FSH, LH, TSH HCG, PTH, Calcitonin ADH (V2 receptors in the DCT) Catecholamines ( receptors) Angiotensin II (epithelial cells in renal tubules) Glucagon b. Phospholipid 2nd messenger system

H + receptor activate G-proteinl (+) phospholipase C Breakdown of P1P2 IP3 Inc. IC Ca++ DAG (+) PKC

Phosphorylates protein This time again a hormone will bind with a receptor on the outer surface of the membrane activating G-proteins. Activated Gproteins will now activate another enzyme system that is phospholipase C that will cause breakdown of phosphoinositol biphosphate (P1P2). One of the breakdown products of P1P2 is inositol triphosphate (IP3) and presence of IP3 increases intracellular calcium. Calcium by itself can function as a 2nd messenger. The other breakdown product of P1P2 is diacylglycerol (DAG), DAG stimulates protein kinase C that will again cause phosphorylation of specific intracellular proteins that will stimulate specific biochemical intracellular reactions. Hormones that use Phospholipase C 2nd messenger system GnRH, GHRH, TRH Oxytocin ADH (V1 receptor in the vascular smooth muscle) Catecholamines ( receptor) A II (vascular smooth muscle) c. Calcium-Calmodulin 2nd messenger system. These are present in the visceral smooth muscle. Steroid hormones are lipid-soluble Cross the cell membrane readily Interact with cytoplasmic receptors Steroid-receptor complex enters the nucleus (+) specific DNAs Production of specific mRNAs Inc. synthesis of specific IC enzymes Mechanism action of steroid hormones: they are lipid soluble, they can readily cross the cell membrane and bind with cytoplasmic receptors and the steroid hormone receptor complex will then enter the nucleus of the cell this time stimulating specific DNAs that will lead to the formation of specific messenger RNAs. The messenger RNAs will move

Adenylyl cyclase cAMP

H + R activate G-protein (+) adenylyl cyclase cAMP (+) protein kinase phosphorylate specific IC proteins (+) biochemical reaction in the cell The other type of membrane receptors are G-protein coupled receptors. Receptors are located on the outer surface of the membrane while G-proteins are on the inner surface of the membrane. Activation of G-proteins will lead to the production of intracellular ligands or what we call second messengers. This second messengers will mediate the action of the hormone on the target cell. What are the different types of second messengers? First we have the adenylyl cyclise cyclic AMP system. A hormone will bind to the receptor on the outer surface of the membrane and that will cause 6 Shannen Kaye B. Apolinario, RMT

out of the nucleus, stimulate the ribosomes to increase the synthesis of specific intracellular protein enzymes. T3 and T4 Interact w/ nuclear receptor

H CRH (+) AP ACTH Aderenla cortex

(+) specific DNAs Cortisol, Androgens Production of specific mRNAs Inc. synthesis of IC enzymes T3 and T4 bind with nuclear receptors again stimulation specific DNAs that will cause the production of specific RNAs. This RNAs will then move out of the nucleus to stimulate the ribosomes to increase the synthesis of intracellular enzymes. Steroid hormones and thyroid hormones can stimulate gene transcription: it simulates DNA and produces mRNA so we can consider these hormones as gene stimulators. So when we say gene stimulators, they are steroid and thyroid hormones. Regulation of Endocrine Secretion 1. Indirect Nervous Control H-H target gland axis Hypothalamus RF/RH (+) AP trophic hormone (+) Target gland hormones True for AP, thyroid, adrenal cortex, ovaries, testes Estrogen Not all layers of adrenal cortex is dependent on ACTH. The hypothalamus will secrete corticotrophin releasing hormone that will stimulate the anterior pituitary gland to secrete corticotropin or ACTH. The zona glomerulosa is ACTH is independent, only the zona fasciculata and zona reticularis are ACTH dependent. (Aldosterone secretion is not dependent on ACTH. The major factor that regulates the secretion of aldosterone is K and RAAS). It stimulates the adrenal cortex but only the two layers and there will be secretion of cortisol and androgenic hormones. H GnRH (+) AP FSH Ovary Progesterone LH

In females, hypothalamus secretes gonadotropin releasing hormone that will stimulate the anterior pituitary gland to secrete FSH and LH. The target gland is the ovary. The ovary will secrete estrogen and progesterone. The cells that produce estrogen and progesterone are different. H GnRH (+) AP FSH Sertoli cell Inhibin LH ICL Testosterone

One mechanism that regulates endocrine function is indirect nervous control via the hypothalamic-hypophyseal target gland axis. The hypothalamus secretes a releasing factor or releasing hormone that will stimulate specific cells of the anterior pituitary gland to secrete specific trophic hormone. This trophic hormone will act on a specific target gland to cause the secretion of a hormone that is why it is called hypothalamichypophyseal target gland. This is the mechanism that will regulate the activity of the anterior pituitary gland, thyroid, adrenal cortex, ovaries, and testis. H GHRH (+) AP GH Liver IGF-I GHIH (-)

In males, hypothalamus secretes gonadotropin releasing hormone that will stimulate the anterior pituitary gland to secrete FSH and LH. The target gland is the testis. In the testis, FSH stimulates the sertoli cells so there will be secretion of a little amount of estrogen and another hormone that is inhibin. LH stimulates the interstial cells of Leydig that will secrete testosterone. Regulation of Hormone Secretion a. Negative feedback control Excess free hormone from a target gland will inhibit the hypothalamus and anterior pituitary gland. H GHRH (+) AP GH Liver Inc. IGF-I (-) GHIH (-) (-)

The hypothalamus secretes the growth hormone releasing hormone that will stimulate the anterior pituitary gland to secrete growth hormone. One of the target cell or target organ of growth hormone is the liver. When stimulated, it will produce IGF I or somatomedin C. But remember that the hypothalamus can also stimulate the secretion of growth inhibitory hormone that will now inhibit the anterior pituitary gland from secreting growth hormone. H TRH (+) AP TSH Thyroid gland T3, T4 The hypothalamus secretes thyrotropin releasing hormone that will stimulate the anterior pituitary gland to secrete thyrotropin. Target gland now is the thyroid gland. When stimulated by TSH, it will release T3 and T4. 7 Shannen Kaye B. Apolinario, RMT

IGF I can regulate GHRH and GH by exerting a negative feedback effect that is if it is in excess, it inhibits the hypothalamus from secreting GHRH, it inhibits the anterior pituitary gland from producing growth hormone. Everything will decrease and it will return back to

normal. If it go beyond the normal, negative feedback will stop so it will increase again. H TRH AP TSH Thyroid gland T3, T4 If you have TRH, you will have TSH, T3 and T4. If there is an excess free T3, T4, negative feedback will be activated resulting to a decrease in TRH, TSH. If the negative feedback is exerted on the anterior pituitary gland, it is the short loop. If it goes to the hypothalamus, it is the long loop. H CRH AP ACTH Aderenla cortex Cortisol, Androgens Between cortisol and androgens, it is mainly the excess in free cortisol that will have a feedback effect because the androgens produced by the adrenal cortex are weak so if you have excess cortisol, negative feedback will be activated decreased CRH, decreased ACTH. H GnRH AP FSH Ovary Estrogen Progesterone LH (-) (-) (-) (-) (-) long loop (-) short loop

Estrogen also has a positive feedback effect. Excess free hormone from a target gland will further stimulate the hypothalamus and anterior pituitary gland. That is exemplified by an excessive increase in estrogen secretion a few hours before ovulation. So if there is excess in estrogen, positive feedback is activated to the hypothalamus and anterior pituitary gland resulting to further increase in GnRH, FSH, LH and estrogen. Excessive increase in estrogen is the only one that has a positive feedback. In relation to this, you have to know the three levels: hypothalamus, anterior pituitary gland and target gland. In endocrine system disorders, there are three types: primary, secondary and tertiary. If the disorder is primary, the defect is in the target gland. If it is secondary, the problem is in the anterior pituitary gland. If it is tertiary, the problem is in the hypothalamus. So the hormonal pictures are different depending on the condition. T3, T4 Decreased Decreased Decreased Increased Increased Increased TSH Increased Decreased Decreased Decreased Increased Increased TRH Increased Increased Decreased Decreased Decreased Increased

1o hypothyroidism 2o hypothyroidism 3o hypothyroidism 1o hyperthyroidism 2o hyperthyroidism 3o hyperthyroidism

Example, if a patient has primary hypothyroidism, the problem is in the thyroid gland so there is no production of T3 and T4. TRH will now increase because there is no negative feedback. TSH will also increase because there is no negative feedback. Comparing it to secondary hypothyroidism or pituitary hypothyroidism, the first one to decrease is TSH. Because there is no TSH, T3 and T4 will also decrease but TRH will increase since there is no negative feedback. But if it is tertiary hypothyroidism, TRH, TSH, T3 and T4 are all decreased. In primary hyperthyroidism, you have increase T3 and T4 so negative feedback is activated so there is decrease in TRH and TSH. If it is secondary or pituitary hyperthyroidism, there is increase in TSH, increase in T3 and T4, decreased TRH. If it is tertiary hyperthyroidism, increased TRH, TSH, T3 and T4. 2. Modified Negative Feedback Control Independent of the hypothalamus and anterior pituitary gland Negative feedback is not due to excess hormone from a target gland but to a blood metabolite regulated by the hormone True for: PTH, islet of Langerhan, adrenal cortex (aldosterone) Decreased calcium PTH (-) Bone Intestine Kidney Increased Calcium Another mechanism outside of the H-H target gland axis is the modified negative feedback. According to Berne and Levy, it is called the physiologic response driven feedback. This mechanism can regulate hormonal activity without the involvement of hypothalamus and anterior pituitary gland. You have a negative feedback effect that is not exerted by a hormone but it is exerted by a metabolite in the blood. But the blood concentration of that metabolite is regulated by a hormone and this type of mechanism will regulate the activity of the following glands: PTH, islets of Langerhan and adenal cortex (aldosterone). Parathyroid. Hypocalcemia is the major stimulus that will cause the secretion of parathyroid hormone. PTH acts on three target organs: bone, intestine and kidneys and the net effect is to cause hypercalcemia. Hypercalcemia will inhibit further PTH secretion. So you have a negative feedback effect wherein hypothalamus and anterior pituitary gland are not involved and the negative feedback is exerted not

In females, increased progesterone will activate negative feedback going to the anterior pituitary gland but the main effect is in LH secretion. If there is a moderate increase in estrogen which will happen at the beginning of the female monthly cycle, negative feedback will be activated but in the anterior pituitary gland, mainly in the FSH. H GnRH (+) AP FSH (-) Sertoli cell Inhibin LH (-) ICL Testosterone

(-)

In males, increased testosterone activates the negative feedback anterior pituitary gland, mainly LH. It is an increase in inhibin that will have a negative feedback in FSH anterior pituitary gland only so it is short loop. b. Positive Feedback Control Excess free hormone from a target gland stimulates the hypothalamus and anterior pituitary gland H GnRH (+) AP FSH Ovary Estrogen Progesterone LH

Shannen Kaye B. Apolinario, RMT

by a hormone but by a metabolite in the blood, in this case it is calcium. Calcium will inhibit PTH secretion but the plasma calcium level is regulated by PTH. Insulin and glucagon. The metabolite is blood glucose. If the blood glucose is high, insulin secretion is stimulated to decrease blood glucose level. If it is already low, insulin secretion is inhibited. In aldosterone, it is mainly hyperkalemia. If potassium is increased, aldosterone is secreted to remove potassium thereby decreasing it. 3. Permissive Action of a Hormone PTH Inc. Vitamin D Inc. intestinal absorption of Ca Another mechanism is permissive action of a hormone. This time, hormone A does not act directly on the target cell. Instead, hormone A increases the production of hormone B and hormone B will act on the target cell. So hormone A indirectly acts on the target cell and has a permissive action on hormone B. Example, in parathyroid hormone, we mentioned that one of its target cells is the gastrointestinal tract but is indirect. It can increase intestinal absorption of calcium by increasing the production of active vitamin D. It is vitamin D that will directly increase intestinal absorption of calcium. So PTH indirectly increases intestinal absorption of calcium and PTH has a permissive action on vitamin D. 4. Direct Nervous Control Sympathetic preganglionic fibers (+) Adrenal medullary cells (+) Secretion of catecholamines Impulses from hypothalamus (+) Posterior pituitary gland (+) Release of stored ADH (oxytocin)

There are two endocrine glands whose activities are under direct nervous or neural control: adrenal medulla and posterior pituitary gland. Remember there are some sympathetic pre-ganglionic fibers that will synapse with the adrenal medullary cells and the adrenal medullary cells are histologically similar to a sympathetic ganglion so that when the sympathetic nervous system is stimulated, the adrenal medulla is also stimulated to release epinephrine and norepinephrine. The other one is the posterior pituitary gland which is an outgrowth of the hypothalamus so that nerve impulses from the hypothalamus will be transmitted by nerve fibers to the posterior pituitary gland and that will cause the release of either ADH or oxytocin.

This is the confidence we have in approaching God: that if we ask anything according to His will, He hears us. And if we know that He hears us whatever we ask we know that we have what we asked of Him. -1 John 5: 14, 15 GOD BLESS YOU 9 Shannen Kaye B. Apolinario, RMT