Physiology Lecture 25

Puberty and Reproductive Years

• Puberty establishes functional and structural maturation through the hypothalamic-pituitary-gonadal axis.
• Sex hormones control synthesis and mechanisms.
• Menstrual cycles are a key aspect of this process.

Gonadal Sex: Testes

• Germ cells produce sperm.
• Leydig cells release testosterone.
• Sertoli cells support germ cell development and release inhibin.

Gonadal Sex: Ovaries

• Germ cells produce eggs (ova).
• Granulosa cells support egg development and release estrogen.
• Theca cells produce androgens, precursors to estrogen.

Hormone Function in Testes

• Supporting sperm maturation, testosterone synthesis, and secretion of anti-Müllerian hormone.

Hormone Function in Ovaries

• Development and maturation of ova.
• Synthesis and secretion of estrogen and progesterone.

Male Genitalia

• The epididymis is where sperm mature and gain motility.
• The vas deferens propels sperm during ejaculation.

Female Genitalia

• Fallopian tubes transport ova from ovaries to uterus; site of fertilization.
• Uterus is a muscular organ where fertilized eggs implant and develop into fetuses.
• Upper one-third of the vagina is part of the birth canal and involved in sexual reproduction.

Male External Genitalia

• Penis is involved in sexual intercourse and urination.
• Scrotum houses and protects testes, regulating temperature for sperm production.

Female External Genitalia

• Clitoris is a sensitive organ for sexual pleasure.
• Labia majora are outer folds of skin protecting vaginal opening.
• Labia minora are inner folds surrounding the vestibule and clitoris.
• Lower two-thirds of the vagina is the external part, involved in intercourse and childbirth.

Y Chromosome

• Determines male gonadal and phenotypic sex.
• Contains the testis-determining gene.
• Presence of the Y chromosome differentiates male phenotype.

Factors Influencing Sex Differentiation

• Testes presence drives male phenotype differentiation.

• Sertoli cells produce AMH, inhibiting development of female reproductive structures.

• Leydig cells produce testosterone promoting the development of male genitalia.

Female Phenotype Differentiation

• Independent of ovary presence.
• Dependent on absence of testes and corresponding hormones.
• Sex duct system develops differently in females than males.

Sex Hormone Production and Conversion

• Progesterone is converted into testosterone by CYP17 enzyme (17a-hydroxylase/17,20 lyase).
• Testosterone is converted into estrogen by aromatase.
• Testosterone is converted into DHT by 5α-reductase.

Male vs. Female Estrogen

• In males, testicular aromatase-induced estrogen is primarily involved in spermatogenesis.
• In females, estrogen is primarily released from the ovaries.

Aromatase Enzyme

• Found in gonads, skin, adipose tissue, blood vessels, and muscles.
• Converts testosterone into the potent estrogen 17β-estradiol (E2).

Androgenic Effects

• Circulating estrogen affects males and females.
• Influences peripheral tissues in males and ovaries in females.
• Important role in skeletal health, with estrogen promoting osteoblast survival and inhibiting osteoclasts.

Testosterone Physiological Functions

• Responsible for male phenotype, spermatogenesis, and all androgenic responses during fetal development.

Sertoli Cell Functions

• Produces anti-Müllerian hormone for male phenotype development in the embryo.

GnRH (Gonadotropin-Releasing Hormone)

• Initiates puberty, predominantly released in pulsatile manner during sleep.
• Its release pattern (5–25 minutes every 60–90 minutes) is crucial for receptor replenishment and effective hormone signaling.
• Stimulates FSH (follicle-stimulating hormone) and LH (luteinizing hormone) secretion.

LH (Luteinizing Hormone)

• Secretion best matches pulsatile pattern of GnRH.
• Plays key role during puberty in stimulating sex hormone production and secretion.

Sex Hormone Regulation: Feedback

• Testosterone reaches desired levels, suppressing GnRH secretion and anterior pituitary LH release.
• Negative feedback mechanisms regulate hormone production and secretion.

Inhibin and LH Receptors

• Inhibin produced by Sertoli cells reduces anterior pituitary FSH secretion.
• Theca and granulosa cells contain LH receptors.

Progesterone and Androgen Production

• Androgens from Theca cells diffuse to Granulosa cells.

• FSH stimulates aromatase conversion into estrogens.

• Released into bloodstream in both males and females.

Negative Feedback in Females

• Progesterone and estrogen provide negative feedback on hypothalamus and anterior pituitary.

Female Positive Feedback

• High estrogen levels activate positive feedback on hypothalamus and anterior pituitary, surge of LH and FSH.
• Granulosa cells release activin to enhance FSH production, triggering ovulation.

Ovarian Cycle Phases

• Follicular Phase (Days 1-14): FSH and estrogen dominate, follicle growth, and endometrium preparation.
• Ovulation (Day 14): Surge in LH triggers oocyte release.
• Luteal Phase (Days 14-28): Progesterone dominates, preparing for possible implantation.

LH Surge and Ovulation

• LH surge is necessary for ovulation.
• Estrogen feedback, initially negative, becomes positive before ovulation.

Post-Ovulation Changes in Theca and Granulosa Cells

• Theca and granulosa cells luteinize, converting to luteal cells.
• Corpus luteum formation secretes progesterone and estrogen.

Luteal Phase Estrogen/Progesterone Difference

• Lack of CYP17 enzyme for converting progesterone to estrogen.
• Increased inhibin, limiting FSH and estrogen stimulation, leads to higher progesterone relative to estrogen during the luteal phase.

No Fertilization

• If no fertilization, progesterone and estrogen decline.
• Negative feedback is lifted, increasing FSH and LH, stimulating new follicle development.
• Endometrium sheds (menstruation).

Uterus Cycle Phases

• Proliferative Phase: Estrogen causes endometrial thickening, favorable environment for sperm.
• Secretory Phase: Progesterone thickens endometrial lining preparation for possible implantation.

Additional factors

• Cervical mucus becomes viscous and acidic, creating less favorable environment for sperm.
• Prostaglandins (PGs) are released, initiate shedding of the endometrium, and cause vasodilation during menstruation.