5.6 Reproductive endocrinology

The endocrine system plays a crucial role in reproductive function. Hormones like GnRH, FSH, and LH regulate the development of sex organs and gametes. These hormones work together in a complex feedback system, ensuring proper reproductive function in both males and females.

Sex hormones like estrogen, progesterone, and testosterone drive the development of secondary sexual characteristics and maintain reproductive health. Understanding these hormones is key to grasping how the body regulates fertility, pregnancy, and overall reproductive wellness throughout life.

Hormones in reproductive function

Gonadotropins and their effects

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• Gonadotropin-releasing hormone (GnRH) secreted by the hypothalamus stimulates the anterior pituitary to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
• FSH stimulates the development of ovarian follicles in females (folliculogenesis) and spermatogenesis in males
• LH triggers ovulation and the production of estrogen and progesterone in females, and stimulates testosterone production in males (Leydig cells)
• Inhibin, produced by the gonads (ovaries and testes), provides negative feedback to the pituitary, reducing FSH secretion

Sex hormones and their roles

• Estrogen, primarily produced by the ovaries, promotes the development of female secondary sexual characteristics (breast development, fat distribution), regulates the menstrual cycle, and maintains pregnancy
  • Also plays a role in bone health (maintains bone density) and cardiovascular function (promotes vasodilation)
• Progesterone, produced by the corpus luteum and placenta, prepares the uterus for implantation (decidualization) and helps maintain pregnancy
  • Also plays a role in breast development and the regulation of the menstrual cycle (promotes endometrial thickening)
• Testosterone, produced by the testes, promotes the development of male secondary sexual characteristics (muscle growth, deepening of voice), stimulates spermatogenesis, and maintains libido and erectile function
• The decline in estrogen and progesterone levels during menopause leads to the cessation of menstrual cycles and associated symptoms such as hot flashes, vaginal dryness, and osteoporosis

Hypothalamic-pituitary-gonadal axis

Components and their interactions

• The hypothalamic-pituitary-gonadal (HPG) axis is a complex neuroendocrine system that regulates reproductive function in both males and females
• The hypothalamus secretes GnRH in a pulsatile manner, which stimulates the anterior pituitary to release FSH and LH
• FSH and LH act on the gonads (ovaries in females and testes in males) to stimulate the production of sex hormones (estrogen, progesterone, and testosterone) and gametogenesis (oogenesis and spermatogenesis)

Feedback loops and homeostasis

• Sex hormones provide negative feedback to the hypothalamus and pituitary, regulating the secretion of GnRH, FSH, and LH to maintain homeostasis
  • High levels of estrogen and progesterone inhibit GnRH, FSH, and LH secretion
  • High levels of testosterone inhibit GnRH and LH secretion
• Disruptions in the HPG axis can lead to reproductive disorders such as hypogonadism (reduced gonadal function), infertility, and polycystic ovary syndrome (PCOS)

Phases of menstrual cycle

Follicular phase and ovulation

• The menstrual cycle is a series of physiological changes that occur in the female reproductive system, typically lasting 28 days, in preparation for potential pregnancy
• The follicular phase (days 1-14) begins with menstruation and is characterized by rising levels of FSH, which stimulates the development of ovarian follicles and the production of estrogen
• Rising estrogen levels trigger a surge in LH, which induces ovulation (the release of a mature oocyte from the dominant follicle) around day 14

Luteal phase and menstruation

• The luteal phase (days 15-28) begins after ovulation, with the formation of the corpus luteum from the remnants of the ovulated follicle
  • The corpus luteum produces progesterone and estrogen to prepare the uterus for potential implantation (secretory phase)
• If fertilization and implantation do not occur, the corpus luteum degenerates, causing a decline in estrogen and progesterone levels
  • This hormonal withdrawal triggers menstruation (shedding of the endometrium), marking the beginning of a new cycle
• Menstrual disorders such as amenorrhea (absence of menstruation), dysmenorrhea (painful menstruation), and menorrhagia (heavy menstrual bleeding) can occur due to hormonal imbalances or underlying reproductive conditions

Spermatogenesis and male hormones

Stages of spermatogenesis

• Spermatogenesis is the process of producing mature sperm cells (spermatozoa) in the seminiferous tubules of the testes
• Spermatogonia (stem cells) undergo mitotic divisions to produce primary spermatocytes, which then undergo meiosis I to form secondary spermatocytes
• Secondary spermatocytes complete meiosis II to produce haploid spermatids, which differentiate into mature spermatozoa through the process of spermiogenesis

Hormonal regulation of male reproductive function

• FSH stimulates Sertoli cells to support and nourish developing sperm cells, while LH stimulates Leydig cells to produce testosterone
• Testosterone is essential for the maintenance of spermatogenesis, the development of male secondary sexual characteristics (muscle mass, body hair), and the regulation of libido and erectile function
• The hypothalamic-pituitary-gonadal axis regulates male reproductive function through negative feedback loops involving testosterone and inhibin
• Disorders of male reproductive function can include hypogonadism, erectile dysfunction, and infertility due to factors such as hormonal imbalances, genetic abnormalities (Klinefelter syndrome), or environmental toxins

Hormonal changes during pregnancy

Hormones supporting early pregnancy

• Pregnancy is a complex physiological process that involves significant changes in the female reproductive system, as well as adaptations in various other organ systems to support fetal development
• Human chorionic gonadotropin (hCG), produced by the developing embryo (syncytiotrophoblast), maintains the corpus luteum, which continues to produce progesterone and estrogen to support the early stages of pregnancy
• The placenta, which develops from the chorion and maternal uterine tissue (decidua basalis), takes over the production of progesterone and estrogen by the end of the first trimester, maintaining the pregnancy and supporting fetal growth and development

Hormonal effects on maternal physiology

• Estrogen promotes uterine growth, increases uterine blood flow, and stimulates the development of the mammary glands in preparation for lactation
• Progesterone maintains the uterine lining (decidua), prevents uterine contractions, and suppresses the maternal immune response to prevent rejection of the fetus
• Relaxin, produced by the corpus luteum and placenta, softens the cervix and relaxes the pelvic ligaments in preparation for childbirth
• Prolactin, produced by the anterior pituitary, stimulates milk production in the mammary glands
• Oxytocin, released by the posterior pituitary, stimulates uterine contractions during labor and promotes milk let-down during breastfeeding

Hormonal changes during labor and delivery

• The initiation of labor involves a complex interplay of hormonal changes, including a decrease in progesterone levels (progesterone withdrawal), an increase in estrogen and prostaglandin production, and a surge in oxytocin secretion
• Prostaglandins, produced by the fetal membranes and maternal decidua, soften the cervix and promote uterine contractions
• The fetal hypothalamic-pituitary-adrenal axis plays a role in the initiation of labor by increasing cortisol production, which stimulates placental estrogen synthesis and decreases progesterone levels
• Complications during pregnancy, such as gestational diabetes (insulin resistance), preeclampsia (hypertension and proteinuria), and preterm labor, can arise due to hormonal imbalances or other underlying factors