Reproduction
I.  Male Reproduction

A.  Hypothalamic-Pituitary-Testis Axis
1.  Hypothalamus releases GnRH which acts on anterior pituitary gland to cause release of gonadotropins (LH & FSH).  FSH and LH act on testis.
2.  LH stimulates testosterone production by Leydig cells.  Testosterone has negative feedback effect on LH.
3.  FSH stimulates sperm production, maintains Sertoli cells (which are the “nurse” cells for growing spermatazoa) and stimulates androgen binding protein (which is essential to maintain high local concentrations of testosterone within the testis)


B.  Structure of the testis
1.  Leydig cells-site of testosterone production located outside seminiferous tubules
2.  Seminiferous tubules
-composed of Sertoli cells which line lumen of tubule
3.  Seminiferous tubules empty into epididymis


C.  Effects of testosterone
1.  Prior to birth
a.  masculinization of reproductive tract, external genitalia, descent of testes
2.  After birth
a.  growth and maturation of entire male reproductive system
b.  libido
c.  secondary sex characteristics
-hair growth patterns, thick skin, deep voice, etc
d.  protein anabolic effect
e.  bone growth
3.  necessary for sperm production


D.  sperm production
-developing spermatazoa start at base of Sertoli cells and are expelled into lumen of tubule when spermatogenesis is complete
-Sertoli cells nourish sperm and serve as the target of FSH action
-both FSH and testosterone are necessary for sperm production


II.  Female Reproduction


A.  Ovary Structure
1.  Follicle
a.  contains oocytes
b.  provides nourishment for the oocyte
c.  produces steroid hormones
d.  components are:
oocyte
granulosa cells
theca layers
2.  Interstitial cells
3.  Corpus luteum
a.  formed from the remnants of ruptured follicles after ovulation
b.  produce progesterone (essential for maintaining pregnancy during first trimester)


B.  Hypothalamic-Pituitary-Ovary axis
1. similar to male
2. GnRH released by hypothalamus which acts on anterior pituitary to cause release of LH & FSH.  LH & FSH act on ovary.
3. LH
a.  stimulates androgen production by theca (which is a necessary precursor for estrogen synthesis by granulosa)
b.  LH also acts on corpus luteum (CL) to stimulate progesterone production
c.  LH released in large amounts (LH surge) triggers ovulation
4.  FSH
-stimulates ovarian follicle growth
-stimulates estradiol production by granulosa cells


C.  Follicle growth
1.  Prior to follicle formation
a. migraiton of primordial germ cells in embryo yolk sac to genital ridge
b.  initiation of oocyte meiosis
-what is meiosis
-stages of meiotic arrest
-overcome first meiotic arrest with the LH surge
-overcome second meiotic arrest with fertilization by sperm
2.  primordial follicle
-oocyte surrounded by single layer of flattened granulosa cells
-forms resting (non-growing) pool
-steroidogenically inactive
3.  primary follicle
-oocyte surrounded by single layer of cuboidal granulosa cells
-represents first stage of growth
4.  multilaminar follicles
-oocyte with multiple layers of granulosa cells
-granulosa cells are dividing
-granulosa cells are acquiring FSH receptors
-follicles acquire theca layer
-follicles are steroidogenically active (theca makes androgen precursor which diffuses into granulosa cells where it is converted to estradiol by the action of aromatase enzyme)
5.  Antral follicles
-granulosa cells begin secreting follicular fluid
-forms cavity (antrum) filled with fluid
6.  Preovulatory (Graffian) follicle
-oocyte sits on a stalk of granulosa cells (cumulus granulosa cells)
-large fluid filled antrum
-highly developed theca


D.  Follicular steroidogenesis
1.  Theca
-makes androgen
-androgen production stimulated by LH
-androgen diffuses into granulosa cells
2.  Granulosa cells
-contain aromatase
-convert androgen precursors to estradiol
-FSH stimulates aromatase activity and thus stimulates estrogen production
3.  Need for both theca and granulosa is the 2-cell theory of estrogen synthesis


E.  Fate of individual follicles
1.  Dominant follicle
-in humans one follicle out of the growing cohort of follicles becomes dominant and will ovulate
-a result of the follicle gaining extra gonadotropin receptors,  thus being more sensitive to gonadotropins and outpacing the others ?
2.  Atresia
-most of the follicles which begin growing will not ovulate (thank goodness or we’d be litter-bearing mammals)
-instead undergo follicular death (aka atresia)


F.  The ovarian cycle (see figure 81-3 in textbook)
1.  Follicular phase
a. follicles are growing under influence of FSH
b. estradiol concentrations are increasing
2.  Ovulation
a. increasing levels of estradiol have positive feedback effect on LH
b. LH surge
c. follicles luteinize in response to LH surge
-start producing progesterone instead of estradiol (in preparation for becoming corpus luteum after ovulation)
d. LH surge gets the oocyte through the first meiotic arrest
e.  oocyte and cumulus cells are expelled
3.  Luteal phase
a.  LH from anterior pituitary is sufficient to maintain CL for approximately 12 days.
b.  Luteal regression if CL is not “rescued” by hCG from the fertilized embryo
4.  Menstruation


G.  The uterine cycle
-the uterine cycle follows the ovarian cycle, which makes sense since it is dependent on the different steroids produced during different phases of the follicular cycle
1.  Proliferation phase
a. the endometrium proliferates, becoming thicker
b.  follicular estradiol stimulates proliferation
c.  coincides with the follicular phase
2.  Secretory phase
a. development of secretory glands
b. development of spiral arteries
c. lots of secretions
d. dependent on progesterone (from CL)
e.  coincides with the luteal phase
3.  Menstruation
a.  loss of luteal progesterone following luteal regression leads to sloughing of tissue & loss of blood from spiral arteries


H.  Other functions of estrogen
1.  breast development
2. other secondary sex characteristics
3. skeletal effects
4.  learning and memory
5.  cardiovascular benefits
6.  growth of reproductive tract
7.  fat deposition (in breasts, hips & thighs)