17.8 Gonadal and Placental Hormones

Gonadal hormones drive reproductive development and function in both males and females. These hormones operate within a tightly regulated feedback loop connecting the hypothalamus, anterior pituitary, and gonads. During pregnancy, the placenta becomes a major endocrine organ, producing hormones that sustain the fetus and adapt the mother's physiology.

Gonadal Hormones and Their Functions

Hypothalamic-Pituitary-Gonadal Axis

The HPG axis is the central control system for reproduction. It works through a cascade: the hypothalamus signals the pituitary, which signals the gonads, and the gonads feed back to keep everything in balance.

1. The hypothalamus releases gonadotropin-releasing hormone (GnRH) in a pulsatile pattern.

2. GnRH stimulates the anterior pituitary to secrete two gonadotropins:

   • Follicle-stimulating hormone (FSH) promotes follicle development in the ovaries and spermatogenesis in the testes.
   • Luteinizing hormone (LH) triggers ovulation in females and stimulates testosterone production by Leydig cells in males.

3. The gonads produce sex hormones (testosterone, estrogen, progesterone) that exert negative feedback on both the hypothalamus and anterior pituitary, reducing GnRH and gonadotropin release.

4. Inhibin, produced by the gonads (Sertoli cells in males, granulosa cells in females), specifically suppresses FSH secretion from the anterior pituitary.

This negative feedback keeps hormone levels within a functional range. One notable exception: in females, a surge of estrogen mid-cycle actually triggers positive feedback on LH, causing the LH spike that drives ovulation.

Testosterone and Estrogen Roles

Testosterone is the primary androgen, produced by Leydig cells (interstitial cells) in the testes.

• Stimulates the development and maintenance of male reproductive structures:
  • Prostate gland (secretes fluid that nourishes and protects sperm)
  • Seminal vesicles (produce seminal fluid, a major component of semen)
  • Penis and scrotum
• Promotes secondary male characteristics during puberty:
  • Deepening of the voice due to enlargement of the larynx and thickening of the vocal cords
  • Growth of facial and body hair
  • Increased muscle mass and bone density
  • Growth spurts followed by epiphyseal plate closure
• Also has metabolic effects, including stimulating red blood cell production (erythropoiesis)

Estrogen (primarily estradiol) is the main female sex hormone, produced by granulosa cells of ovarian follicles. The enzyme aromatase converts androgens (like androstenedione) into estrogens, a process that also occurs in adipose tissue and other peripheral tissues.

• Stimulates the development and maintenance of female reproductive structures:
  • Uterus (site of implantation and fetal development)
  • Fallopian tubes (transport oocytes from ovaries to uterus)
  • Vagina and external genitalia
• Promotes secondary female characteristics during puberty:
  • Breast development
  • Widening of the pelvis
  • Redistribution of body fat to hips, thighs, and breasts
  • Skeletal maturation and eventual closure of epiphyseal plates
• Plays a protective role in bone health by inhibiting osteoclast activity, which is why postmenopausal estrogen decline increases osteoporosis risk

Functions of Progesterone

Progesterone is sometimes called the "hormone of pregnancy" because its effects center on preparing for and maintaining a pregnancy.

Menstrual cycle regulation:

• After ovulation, the corpus luteum (the remnant of the ruptured follicle) produces progesterone.
• Progesterone prepares the endometrium for potential implantation by:
  • Increasing blood supply to the uterine lining
  • Stimulating glandular secretions that create a nutrient-rich environment for a fertilized egg
• It inhibits further ovulation during the luteal phase by suppressing GnRH and LH release.
• If pregnancy does not occur, the corpus luteum degenerates, progesterone levels drop, and the endometrium sheds. This is menstruation.

Pregnancy maintenance:

• During early pregnancy, the corpus luteum continues producing progesterone. Around weeks 8–12, the placenta takes over as the primary source.
• Progesterone suppresses uterine smooth muscle contractions, reducing the risk of premature labor.
• It contributes to mammary gland development by stimulating growth of milk ducts and alveoli in preparation for lactation.

Placental Hormones and Their Effects

Placental Hormones and Maternal Physiology

Once established, the placenta functions as a temporary endocrine organ, producing hormones that maintain pregnancy and alter maternal metabolism to support the fetus.

Human chorionic gonadotropin (hCG)

• Produced by syncytiotrophoblast cells of the developing placenta, starting shortly after implantation.
• Its primary role is to maintain the corpus luteum during the first trimester, ensuring continued progesterone production until the placenta can take over.
• hCG rises rapidly in early pregnancy, doubling roughly every 48–72 hours. This rapid rise is what makes it a reliable marker for pregnancy tests (detectable in maternal blood and urine).
• In male fetuses, hCG stimulates fetal Leydig cells to produce testosterone, which drives development of male external genitalia.
• hCG levels peak around weeks 8–10, then decline as the placenta assumes progesterone production.

Estrogen (placental)

• The placenta produces increasing amounts of estrogen throughout pregnancy, with levels peaking near term.
• Stimulates uterine growth and expansion to accommodate the growing fetus.
• Enhances uterine blood flow, ensuring adequate oxygen and nutrient delivery.
• Prepares the mammary glands for lactation by promoting ductal growth.
• Works alongside progesterone to maintain the uterine environment.

Progesterone (placental)

• The placenta takes over progesterone production from the corpus luteum around weeks 8–12. This transition is sometimes called the luteal-placental shift.
• Continues to maintain the endometrium and suppress uterine contractions throughout pregnancy.
• Contributes to mammary gland development, specifically stimulating alveolar growth in preparation for milk production.

Human placental lactogen (hPL)

hPL (also called human chorionic somatomammotropin) is produced by syncytiotrophoblast cells and has major effects on maternal metabolism:

• Promotes lipolysis (fat breakdown) in the mother, making free fatty acids available as an energy source for maternal tissues.
• Increases insulin resistance in the mother, which keeps blood glucose levels elevated and available for fetal uptake. This is why gestational diabetes can develop if the mother's pancreas cannot compensate for the increased insulin resistance.
• Stimulates mammary gland development and prepares for lactogenesis (milk production).
• hPL levels rise steadily throughout pregnancy, correlating with placental mass.