Sapolsky, Chapter 7.   Stress and Reproduction


I.   Hypothalamus

A.       Collection of nuclei that receive neural input from limbic system and brain stem, and are also sensitive to temperature, osmotic signals, amount of glucose in blood, and hormones.

B.       Output is both neural (to other neurons) and neurohormonal (either into blood to anterior pituitary or into systemic blood circulation via post. pit.). 

1.       Secretes releasing or inhibiting factors into capillaries that go to ant. pit., where they control secretion of tropic hormones that are released into general circulation.  For reproduction the main tropic hormone is LHRH (luteinizing hormone releasing hormone) a.k.a. GnRH (gonadotropin releasing hormone).

2.       Site of neurons that send axons down to post. pit.  Neural firing in hypothalamus causes release of these hormones into circulation.

II. Pituitary

A.       Anterior pit.--derived from tissue from roof of mouth that migrates up and joins post. pit. tissue from base of brain that migrates down.  Secretes ACTH, FSH (follicle stimulating hormone), LH (luteinizing hormone), TSH (thyroid stimulating hormone), GH, PRL (prolactin).

        1.       FSH stimulates growth of the ovarian follicle and the production of sperm in the testes.

2.       LH causes the release of the egg and stimulates production of progesterone.  In males LH   

       stimulates secretion of testosterone.

C.       Posterior pituitary--oxytocin & vasopressin released into blood by neural firing of neurons in hypothalamus with axons to post. pit.

III.  Gonads and reproduction

A.    2 functions: produce gametes and produce hormones.

B.       Testes

1.       Seminiferous tubules contain both Sertoli cells and Leydig cells.

2.       Sertoli cells nourish developing sperm in response to FSH.

3.       Leydig cells, in response to LH, produce androgens, which in turn provide negative feedback to hypothalamus and anterior pituitary.

C.       Ovaries

1.       Follicles

a.       At puberty the 2 human ovaries contain 1/2 million immature oocytes, of which only about 450 are ovulated (about 40 years of fertility x 12 mo./yr., minus some at beginning and end).  The rest degenerate.

b.       Each primary follicle consists of an oocyte surrounded by a layer of granulosa (epithelial) cells.  Surrounding the follicle are thecal cells that secrete estrogens.  The primary oocytes have not yet undergone their first meiotic division, which is constantly inhibited by the surrounding granulosa cells.

c.       Secondary follicle consists of an oocyte surrounded by zona pellucidum; granulosa cells proliferate; space around it is filled with fluid rich in steroids; egg becomes larger.

d.        Tertiary follicle: fluid-filled space enlarges, as does egg.

e.       Graafian follicle: just before ovulation

f.      The surge in LH breaks the connections between the primary oocyte and the granulosa cells, which can therefore no longer inhibit the first meiotic division.  Just before ovulation, the primary oocyte undergoes its first meiotic division and the (now secondary) oocyte is released and swept up by the “fingers” of the fallopian tube.  If it is fertilized in the fallopian tube, it will undergo its second meiotic division and undergo numerous cell divisions and implant into the uterine wall.  If it is not fertilized, the cycle begins again.

2.       Corpus luteum: After ovulation granulosa and thecal cells undergo rapid mitosis and are heavily vascularized. Fat globules also appear, and the combination of the fat and vascularization causes a yellow appearance, which gives it the name “yellow body.”  It secretes progestins necessary to prepare uterus for possible pregnancy.

3.        Corpus albacans (white body): no more hormones.  Connective tissue takes over.

D.       Menstrual cycle

1.         Hypothalamus produces LHRH (GnRH).

2.         This is carried to anterior pit. via portal system: causes pit. to release FSH and some LH into blood stream.

3.         FSH stimulates ovary follicle to secrete estrogen (E) into blood.

4.       E exerts negative feedback on hypothalamus and pituitary, decreasing LHRH and FSH.  So far, this is similar to the process in the male.

5.       BUT, by this time the major follicle has grown so large, and needs so little FSH to stimulate it, that it secretes more and more E.  However, the remaining follicles no longer have enough FSH to keep growing, so they degenerate.  That’s why women usually release only 1 egg (secondary oocyte)/mo. 

6.        Eventually, a high enough level of E occurs to trigger a POSITIVE feedback loop at the hypothalamus, resulting in an outpouring of LHRH to ant. pit., which à FSH and LH release.

7.        LH causes the ovum to rupture out of the follicle; the granulosa cells in the remnant of the follicle (corpus luteum) secrete progesterone (P).

8.         The ovum is swept into the fallopian tube by the action of cilia; there it may or may not be fertilized.

 9.  Also, P increases vascular lining of uterus: preparation for implantation of embryo.

10.   P and E also exert negative feedback on hypothalamus, which results in less LH & FSH. Since LH is needed to trigger P release, & since LH is declining, P also declines. If pregnancy ensues, the placenta itself produces gonadotropin (human chorionic gonadotropin, HCG) and eventually, P.

11. Since uterine lining depends on P for its heavy vascularization, it now breaks down and is eliminated as menstrual flow (in primates) or reabsorbed (in most other mammals).

12. NOTE: the only difference in the pattern of endocrine control between males and females is the POSITIVE FEEDBACK RESPONSE TO ESTROGEN by females, resulting in outpouring of LH and FSH when estrogen levels are high enough.

IV.  Males: testosterone and loss of erections

       A.       “Basic off-the-rack male”: LHRHàLHàtestosterone; LHRHàFSHàsperm.

       B.       Stress: decreases LHRH, followed by decreased LH & FSH, then testes close for lunch.

               1.       Both physical and psychological stressors decrease T levels rapidly.

2.        One example: supporters of soccer team that won had higher T levels than did supporters of team  

       that lost. 

       C.    How does stress influence reproductive hormones?

               1.       Endorphins and enkephalins

                      a.       Decrease pain and also inhibit LHRH release. 

                      b.    Also partially responsible for “runner’s high.”

                      c.       Extreme exercise suppresses male and female reproduction.

                      d.    The resultant decrease in estrogen (from testosterone, in men) results in osteoporosis.

               2.       PRL decreases pituitary responsiveness to LHRH. Double whammy: less LHRH dribbling

                      out of the hypothalamus and anterior pit. responding less effectively to it. 

               3.       Glucocorticoids block response of testes to LH. 

       D.    Stress and erections

               1.       Parasympathetic system stimulates erection, in part through production of nitric oxide (NO).

                      a.     NO induces vasodilation; blood-filled corpora cavernosa press against venous outflow,

                             thereby keeping the blood in the penis and producing the erection. 

                      b.       Parasympathetic system also inhibits ejaculation. 

               2.       However, sympathetic system is also activated: à increased heart rate, blood pressure,

                      faster breathing, and eventually ejaculation.  (A deep breath can sometimes activate

                      parasympathetic system and delay ejaculation.)

               3.       Stress:  sympathetic system inhibits parasympathetic:  impotence or premature ejaculation.

               4.       “Psychogenic” impotence diagnosed by electronic pressure transducer (plethysmograph) or by a

roll of stamps! 

               5.       Erections are much more sensitive to stress than is testosterone secretion and sperm production.

V.    Our friend, the hyena

       A.       Females are socially dominant: more muscular, more aggressive, more androstenedione and a clitoris

that looks like a penis (through which she gives birth!).

       B.    In many social mammals, penile erection is a dominance display: “you wave it around in his face to

show what a tough guy you are.”

       C.        Hyenas: Erection is a sign of subordinance, especially when you’re stressed. 

VI.  Females: Lengthened cycles and amenorrhea

       A.    Slight error on p. 110:  LH and FSH do not build up steadily toward ovulation; negative feedback

actually decreases FSH.  It’s the growth and increasing sensitivity of the follicle that results in

increasing the estrogen that triggers the positive feedback that elicits the midcycle LH surge.

       B.       Females have adrenal androgens (mostly androstenedione), which are converted to estrogens by the

aromatase enzyme in fat cells.  (Obese men also convert some of their androgens to estrogens, and

therefore tend to have more breast development than usual.)

C.       Starvation à less fat à less aromatase à less estrogen and more androgen à reproductive problems.

               1.       True for anorexia nervosa as well as involuntary starvation. 

       D.       Stressà endorphins and enkephalins à decreased LHRH release.

               1.       As in males, PRL decreases sensitivity of ant. pit. to LHRH, and glucocorticoids decrease ovary’s

sensitivity to LH à delayed ovulation and less progesterone secretion. 

               2.       Extreme cases à anovulatory amenorrhea. 

               3.       The decrease in estrogen can à osteoporosis and atherosclerosis. (Jay Kaplan: social

subordination in monkeys)

4.       PRL also interferes with progesterone’s effects à decreases likelihood of implantation.

                      a.       PRL is main reason that breast feeding is an effective form of contraception, especially if

done frequently for short times.  

                      b.       In the West: nurse about 6 times/day for about 30-60 min.

                      c.       In Africa: Bushmen are “the original affluent society.” (They hunt and gather a few hours/day

                             and spend much of their time “sitting around chewing the fat.”)  Their spacing of children

(one every four years) is probably due to the fact that women breastfeed for a minute or two

every 15 min, around the clock for 3 years.  Steady production of PRL.  Only about 2 dozen

menstrual periods in her life. Western women have 500 periods.  Sapolsky: May be related to our increased endometriosis. (Environmental estrogens have also been implicated.)

VII. Females: Disruption of libido

       A.    Rats: Stress decreases both proceptive and receptive behaviors. 

       B.       Estrogen via estrogen receptors (ER) à increased sensitivity of brain and periphery to sexual stimuli.

       C.       Primates (incl. humans): adrenal androgens also increase libido. 

VIII. Stress and the success of high-tech fertilization

       A.       Treatment of infertility:  artificial insemination, in vitro fertilization, preimplantation screening (for

genetic defects), donor eggs & donor sperm, injection of sperm into egg.

       B.    2 Problems:

1.       Stressful and “expensive as hell” ($10-15 K/cycle); weeks of painful shots, daily blood draws,

sonograms, emotional roller-coaster, surgical procedure.

2.    It rarely works. (10-20% chance)

       C.       Correlation between high glucocorticoid levels and lower success.  But which came first? 

IX.       Miscarriage and psychogenic abortions

       A.       Competitive infanticide and harassment of pregnant mother to induce miscarriage.

       B.       Rodents: Bruce-Parkes effect in response to new male.

       C.       Pseudo-estrus (fake heat): “sucker the new guy into thinking he’s the father….  Given the appalling

lack of knowledge about obstetrics among most male rodents and primates, it usually works.”)

       D.       Humans: less common.  However, stress reduces blood flow to uterus, similar to effect on intestines. 

Repeated hypoxia to fetus can cause asphyxiation.

X.    How detrimental to female reproduction is stress?

       A.    In concentration camps 54% stopped menstruating, most within the first month, before fat levels


       B.    The wonder is that reproductive physiology still worked at all in almost half the women. Reproduction

can be astoundingly resistant to stress.

       C.    But stress can wreak havoc with the subtle joys.