Which came first - the chicken or the egg? Physiology of Reproduction Jennifer McDonald DO

Hypothalamic Pituitary Axis Neural controlChemical control Dopamine (-) Norepiniphrine (+) Endorphins (-) Hypothalamus Gn-RH Ant. pituitary FSH, LH Ovaries Uterus Progesterone Estrogen Menses –± ?

Sequence of Maturation

Telarche = breast development Estrogen dominant

Tanner Staging - Breast Development PrepubertalBreast bud with areola widening

Enlargement of breast. No separation of contours Secondary mound with separation of contours Mature breast

Adrenarche = pubic hair growth Adrenal androgen dominant DHEA DHEAS

Tanner Staging - Hair Growth No hairStraight along labia Increased quantity, female triangle

More dense, curled, adult distribution Medial aspect of thighs

Timing is Everything

Menarche = onset of menses Average 2 to 2.5 years after breast development Average American girls 12.7 years +/- 1 year Earlier in African American and Hispanic girls Usually delayed until critical mass ~105 pounds or body fat content of 22%

Delayed Puberty No pubertal development by age 13 Pubertal maturation not completed within 4 years or Menses not begun by age 16

Precocious Puberty Breast or pubic hair development before 7 years (Caucasians) or younger than 6 years (African Americans) Most common cause = idiopathic

Menarche Requirements: o GnRH from the hypothalamus o FSH and LH from the pituitary o Estrogen and progesterone from the ovaries o Normal outflow tract

Who’s Doing What Ovary Follicular Phase Ovulation Luteal Phase Uterus Proliferative Phase Secretory Phase

Mature Ovary Non-growing = primordial follicles Growing follicles Primordial follicles are arrested in which stage of meiosis?

15 to 20 weeks gestation as many as 7 million germs cells in each ovary Newborn = 2 million primary oocytes Puberty = 300,000 primary oocytes remain 400 will become secondary oocytes and ovulate during reproductive years Numbers Game

GnRH Gonadotropin releasing hormone Comes from ?? Stimulates ?? What is unique about its release ??

Follicle Stimulating Hormone (FSH) Comes from ?? Release stimulated by ?? Stimulates growth and maturation of follicles Stimulates estrogen production in granulosa cells Inhibited by estrogen and progesterone

Theca interna - androstenedione in response to LH Granulosa cells - convert androstenedione to estradiol when stimulated by FSH

Luetenizing Hormone (LH) Comes from ?? Release stimulated by ?? Also stimulated by high levels of estrogen Inhibited by estrogen & progesterone together Triggers ovulation Maintains the corpus luteum LH surge initiates continuation of meiosis

Ovulation occurs approximately hours after the LH surge and hours after peak estradiol levels attained

Corpus Luteum (“yellow body”) Theca interna & granulosa cells Directed by LH Synthesizes estrogen and significant amounts of progesterone (40 mg/day) Progesterone causes secretory endometrium in preparation for implantation

Indicators of Ovulation Prospective or retrospective? Basal body temperature Urinary LH Serum progesterone Ovum lives approximately 24 hours after it is released but is fertilizable less than half that time

Uterine Cycle

Proliferative Phase Estrogen dominates Parallels follicular phase of the ovary Growth of blood vessels, mucosa and glands Secretory Phase Progesterone dominant Parallels luteal phase Mucous producing

Normal Menstruation Predominantly arterial Usual duration 3-5 days 1 to 8 days still normal Average flow 30 mL More than 80 mL abnormal

Cervical Changes Estrogen - thins Progesterone - thickens Spinnbarkeit Fern Patterns

Breast Changes Estrogen - proliferation of ducts Progesterone - growth of lobules & alveoli Mastalgia = cyclic breast pain

Estrogens Estrone (E1) 17  -estradiol (E2) Estriol (E3) Which organs/cells are responsible for production of estrogen? Granulosa cells, theca cells, corpus luteum, and the placenta

Estrogens 17  -estradiol is the major secreted estrogen Estradiol is the most potent Estriol is the least potent 2% of circulating estradiol is free

Progesterone Secreted in large amounts by the corpus luteum and the placenta 2% free in circulation Important intermediate in steroid biosynthesis pathway Fluctuate widely during cycle What does progesterone do?

Testosterone Secreted by ovaries, adrenal cortex (small) and peripheral conversion androstendedione (half) Follow Circadian rhythms What time of day is testosterone its highest?