Transcribed by Jazmin Lui May 10 2014

ORGAN SYSTEMS PHYSIOLOGY OF REPRODUCTIVE SYSTEM II DR. SCHIFF

1. Intro: 3 cycles regulating female reproduction processes
Ok good morning. Today well be talking about the more interesting half of
the population. And certainly from a physiology point of view the more
complicated part of the population. After all, basically once you have an adult
male all thats required for him to be fertile, is for someone to say yes
(laughter). But in women the reproduction processes are much more
complicated. And its been likened to a 3 ring circus because theres 3 things
happening and theyre all synchronized. What youve got is changes in
hormone levels related to changes in the ovaries. Youve got changes in the
ovaries themselves related to ovulation, which Dr. Lopez went through. And
there are also changes in the uterus to prepare it for possible implantation of
a fertilized egg having become an embryo. And all of these things are going
along in synchrony over a periodic cycle that runs about 28 days, more or
less. So you have a uterine cycle, you have a hormonal cycle and you have an
ovarian cycle. Now Im not going to spend too much time on the ovarian
cycle in terms of maturation of follicles and the like, and eventually ovulation,
except to refer you back to what Dr. Lopez said.

2. Hormonal cycle
What you have in the hormonal cycle, which gets a little complicated
compared to that of the males, is basically you have the hypothalamus
releasing some gonadotropin releasing hormones, there seems to be an LH
releasing hormone and an FSH releasing hormone but these are generally all
secreted simultaneous so what youve got here is, sort of lumped together as
gonadotropin releasing hormone. And they then act on the gonadotropes in
the pituitary, some of which produce LH and some of which produce FSH. At
this point there is no big difference between male and female, the scheme up
to this point is identical. Now what then happens, is you have the follicular,
oh Im skipping here, what you then have is the follicular development which
Transcribed by Jazmin Lui May 10 2014

eventually leads to theca cells and granulosa cells, which roughly correspond
to the Leydig and Sertoli cells in the male. But, not really, just that there are
two different types of cells and the theca cells are generally stimulated by LH
and FSH generally stimulates the granulosa cells. And when this develops
eventually into a corpus luteum youll have theca luteum and granulosa
luteum cells. Now in the male, life is simple, the Leydig cells secrete
testosterone, period. And thats where the hormones come from. The
corresponding hormones, the estrogens, specifically estradiol, cant be made
by theca cells or granulosa cells. Neither one alone is capable of synthesizing
the hormone. What youve got is, the theca cellsboth are capable of taking
the first few steps in the synthesis. Then, this sort of dead ends here. But
since the cells are physically next to each other they can share what theyve
made. And at this particular point let me save myself some walking and
leave the specific notes here youve got pregnenolone which is a dead end
in the granulosa cells but can be sent over to the theca cells which are also
capable of making pregnenolone. The theca cells can then take the
pregnenolone a few more steps to produce androgens, that is DHEA,
androstenedione, and thats a dead end as far as the theca cells are
concerned. But the androgens can then shift back, shared again, to the
granulosa cells, and the granulosa cells can take these androgens and with
and aromatase, and by androgens I mean those same androgens produced in
the adrenal cortex, in the zona reticula, but also testosterone. And those
androgens including testerone, are subject in the granulosa cells, to an
aromatase which produces estrogens, including in the case of testosterone,
estradiol. So basically what youve got here, in the ovary and eventually in the
corpus luteum are 2 different kinds of cells, that between them can make
these different kinds of hormones, these estrogens, specifically estradiol.
Now, its a little more complicated, also, because once youve got these
estrogens, in particular estradiol, you have a feedback loop because this is the
hypothalamic pituitary axis, and theres a sort of feedback here. But you may
notice I didnt put a minus sign and a circle. Strange things happen in these
Transcribed by Jazmin Lui May 10 2014

female people. Most of the time its your standard inhibition. But sometimes it
switches into a positive feedback. And the mechanism for that switch, which
obviously, since estradiol is estradiol, the change somewhere is in the pituitary
gonadotropes and somehow they undergo some sort of change, or its been
suggested that there may be multiple estradiol receptors in these
gonadotropes and you know, when I was discussing dopamine and
sometimes at low concentrations you get a vasodilation but at higher
concentrations you get vasoconstriction? When I was talking about the
afferent arteriole in the kidney? See how this whole course comes together?
Just like a final exam (nervous laughter). Something changes here and at
specific times in the cycle, this is sometimes a plus, a positive feedback. And
well go through that in a minute.



3. Hormonal levels over 28 day female cycle

Transcribed by Jazmin Lui May 10 2014


Lets go to the first diagram that I stuck into the handout. Basically its a
diagram of an approximately 28 day cycle. And I think just as I did there,
youre going to have, were gonna need some colours, I dont know how you
take notes but youve got the handout. Were referring to a 28 day cycle, or
29 or 30, theyre different in different women. It really has no relationship to
the moon. Early people considered that hey, this is 28 or 29 days, the
phases of the moon, must be a link. A post hook ergo proctor hook
argument, if it follows it must be caused by which is false. And generally to
define this 28 day cycle, day 1 is referred to as the beginning of the
menstrual flow. So what youve got here is, first of all theres the sloughing of
the uterine lining of the uterus, and youre assuming theres no pregnancy
here, cause then wed stop cycling if there is pregnancy. But theres the
sloughing of the uterine flow, but meanwhile the LH and FSH levels are kind
of low and are sinking lower, ok? So well say FSH and LH, which are
produced in the pituitary and travel through the circulation, theyre kind of
low, but FSH and LH stimulate the production of the estrogens including
estradiol. So as long as theyre here at all, estradiol levels are slowly rising.
Transcribed by Jazmin Lui May 10 2014

And as you go on, up to about day 8, 14, so lets set up this axisso lets say
up to about day 10, so up to about here the estradiol is creeping up. And the
more estradiol there is, it inhibits, theres that minus sign, it inhibits the
gonadotropes, so the LH and FSH keep going down. OK? Now, something
happens around day 10. And this minus changes to a plus. And this is one of
the few places in the body, well the first one you ever saw was in sodium
channels and excitable tissue, where depolarization increases sodium
permeability which further depolarizes the cell. This is positive feedback. There
are very few instances of positive feedback in the body because in general
homeostasis is maintained by negative feedback. But heres positive feedback.
Now, estradiol, which is high, stimulates FSH and LH secretion. So the FSH
heads up, the LH heads up even more so, and because theyre going up the
estradiol is going up even more so. So from day 10 up to about, wheres the
eraser, I made them a little steeper than they ever would be in real life, lets
just slow this down a little bit, and estradiol is going up up up until about day
13. And about day 13, that plus changes back into a minus. So something
happened for about 3 days that led to positive feedback between the
estradiol and gonadotropes. Now, the estradiol has gotten even higher
because of the high LH and FSH concentrations, so now estradiole is way up
there. This now inhibits their production so they head back down after going
through a peak at about day 14 they go back down. And when they go down,
the estradiole heads back down. But meanwhile, just before day 14 there was
this enormous surge of FSH and LH. LH in particular leads to rupture of the
Graafian follicle, which is ovulation. So right here on day 14 in this ideal
predictable cycle, in which everything happens exactly according to clockwork,
which is why they used to call couples you used rhythm method of
contraceptive, parents. Theres always a little variation here. So this goes
down, youve got this peak of LH and FHS, theyre going down. But
meanwhile, the LH, luteinizing hormone, its called luteinizing hormone
because it promotes the formation and maintenance of a corpus luteum.
Whats a corpus luteum? Well after the follicle ruptures and just before
Transcribed by Jazmin Lui May 10 2014

ovulation this Graafian follicle has gotten pretty big compared to the size of
the ovary. The remaining lining of the Graafian follicle forms what is known as
corpus luteum, which is the word for yellow body. Corpus is body, luteum
refers to yellow. And corpus luteum can cover like, if you look at an ovary,
about a 1/3 of it, its enormous! And as long as the corpus luteum has
formed, it starts producing, of all strange things, estradiol. So the estradiol
starts going up again. Now the corpus luteum, unlike the ovary before
ovulation, is also capable of producing progesterone. So heres your estradiol,
again, so you keep track of the curves, theres essentially no progesterone
formed along here, but once the corpus luteum forms the progesterone goes
up. So you have estradiol up, progesterone up, and what do the estradiol and
progesterone do? They A) inhibit the production of LH and FSH. So these
fellows keep going down and down. And B) they promote the thickening of
the endometrium, the vascularization, and all of the things that Dr. Lopez
described in terms of going on in the uterine lining. So you have this
thickening and increased vascularization of the uterine lining, so that if the
egg thats been kicked out, happens to be fertilized, itll have a nice place to
land.

4. Ovulation process (ovary uterus)
Now, heres the egg, shoots out the surface of the ovary, and somehow its
collected into the oviducts or fallopian tubes. Now how does that happen?
Well the fallopian tubes come up to the ovary and partially surround it with
finger like projections called fimbriae. And around the time of ovulation these
fimbriae grow, and extend to cover more and more of the surface area. They
also have cilia on their inner surface, the surface towards the lumen of the
fallopian tube, which wave and create a fluid current, from ovary towards
down uterus. Because the egg that formed during ovulation, unlike the sperm,
dont have a tail. So they cant swim. They just passively go with the flow, the
current flow of fluid within the fallopian tubes. And the cilia in the fimbriae
wave it towards the opening of the fallopian tube, and there are further cilia
Transcribed by Jazmin Lui May 10 2014

lining the fallopian tube that create current flow, down towards the uterus
and that carries the egg along. So now youve got the egg, heading towards
the uterus. Now, there are all sorts of things going on, at this particular time
interval. It takes 3-4 days for the egg to reach the uterus with this passive
flow.