Hormones of Reproduction: an Overview

Gonadotropins

Hormones released by the anterior pituitary gland that regulate the activity of the testes and ovaries. The two main gonadotropins are luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

What are the functions of LH and FSH?

LH and FSH stimulate the gonads to produce sex steroid hormones like testosterone and estrogen.

• LH and FSH are heterodimeric glycoproteins, meaning they are made of two subunits—an alpha subunit and a beta subunit.

How do sex steroids affect LH and FSH secretion?

Sex steroids exert negative feedback on the anterior pituitary, inhibiting further secretion of LH and FSH.

Gonadotrophs

Specialized cells in the anterior pituitary that synthesize and secrete LH and/or FSH. Most produce only one of the hormones, but some can secrete both.

What determines the biological function of LH and FSH?

The beta subunit, which is unique to each hormone, determines its biological specificity and function. The alpha subunit is identical across all glycoprotein hormones in this family.

Glycoprotein hormone family

A group of anterior pituitary hormones that includes LH, FSH, thyroid-stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH), all of which share a common alpha subunit.

What roles do LH and FSH play in males and females?

LH and FSH stimulate the gonads to produce sex steroids. In males, LH acts on Leydig cells to produce testosterone. In females, LH stimulates theca cells to make testosterone, which is then converted to estrogen by granulosa cells under FSH stimulation.

Follicular steroidogenesis

A two-cell hormone production process in females where theca cells make testosterone (LH-stimulated), and granulosa cells convert it to estrogen (FSH-stimulated), primarily in healthy growing antral follicles.

What is the preovulatory gonadotropin surge, and what does it trigger?

It’s a sudden, substantial increase in LH and FSH secretion that triggers ovulation of mature ovarian follicles.

What is the corpus luteum, and how is it formed?

After ovulation, remaining follicular cells form the corpus luteum, which secretes progesterone and estradiol (in primates). LH promotes this luteinization process.

• LH supports the growth, maintenance, and function of the corpus luteum. FSH stimulates the growth of antral follicles that have entered the fluid-filled stage.

What effect does administering high doses of FSH have in humans and animals?

It induces the growth of multiple mature follicles, increasing the number of mature gametes available for ovulation.

What role does FSH play in the male reproductive system?

In males, FSH supports spermatogenesis by maintaining the function of Sertoli cells, which provide structural and nutritional support to developing sperm in the seminiferous tubules.

GnRH (Gonadotropin-Releasing Hormone)

A hormone produced by specialized neurons in the arcuate nucleus of the hypothalamus; it stimulates the anterior pituitary to release LH and FSH.

Through what system does GnRH travel from the hypothalamus to the anterior pituitary?

GnRH is released into the hypophyseal portal system, a network of blood vessels connecting the hypothalamus to the anterior pituitary.

How does GnRH stimulate LH and FSH release in the anterior pituitary?

GnRH binds to G-protein coupled receptors (GPCRs) on gonadotrophs, the hormone-producing cells in the anterior pituitary.

• GnRH is secreted in pulsatile bursts, with frequency varying from a few pulses per day to more than one per hour, depending on physiological needs.

How do the frequency and amplitude of GnRH pulses affect LH and FSH secretion in females?

High-frequency, high-amplitude pulses of GnRH stimulate LH secretion, while low-frequency pulses tend to promote FSH secretion.

Estrous/Menstrual Cycle and GnRH Release

During the follicular phase, rising estradiol stimulates the hypothalamus, causing a GnRH surge that rapidly increases LH and FSH secretion (positive feedback). During the luteal phase, progesterone and estradiol exert negative feedback, suppressing GnRH secretion.

How is GnRH secretion different in males compared to females?

In males, GnRH is secreted in pulses at a relatively steady frequency, and elevated testosterone exerts negative feedback on the hypothalamus to regulate LH and FSH secretion.

• Sleep, physical activity, stress, and other hormones can influence GnRH secretion.

the gonads produce two important hormones

1. Inhibin

2. Activin 

• These help fine-tune the reproductive hormone system. These hormones specifically target the anterior pituitary to regulate the secretion of FSH

  • Inhibit works to decrease FSH secretion

  • Activin works to stimulate FSH secretion. 

How does high prolactin during lactation affect reproductive hormones?

High prolactin suppresses GnRH activity, leading to decreased LH and FSH secretion, causing delayed ovulation in the anovulatory postpartum period.

Anovulatory Postpartum Period

The phase after childbirth when ovulation is delayed due to suppressed GnRH from high prolactin levels during lactation.

What is human chorionic gonadotropin (hCG) and where is it produced?

hCG is a hormone produced by trophoblast cells of the early embryo starting about 8–9 days after fertilization, not by the pituitary gland.

• hCG prevents degeneration of the corpus luteum, ensuring continued progesterone production essential for maintaining early pregnancy.

• hCG stimulates Leydig cells in the testes to produce testosterone, supporting male fetal development.

Prolactin (Prl)

A single-chain protein hormone, structurally similar to growth hormone, secreted mainly by lactotroph cells in the anterior pituitary and other tissues like the brain, immune cells, and the decidua.

• Stress and environmental factors can suppress prolactin synthesis.

What is mammogenesis and how is prolactin involved?

Mammogenesis is the lobuloalveolar development of mammary glands, where alveoli (milk-secreting cell clusters) form and develop under the influence of prolactin.

How does prolactin contribute to lactogenesis (milk production)?

Prolactin, along with cortisol and insulin, promotes uptake of amino acids, sugars, and fats, initiating gene transport that encodes milk proteins necessary for milk production.

Prolactin Regulation

Prolactin secretion is tonically inhibited by dopamine, but can be stimulated by hormones like TRH, GnRH, VIP, and nipple suckling activates a spinal reflex arc that leads ti the release of replication-stimulating hormones from the hypothalamus resulting in increased prolactin secretion.

How do rising estrogen levels affect prolactin during pregnancy?

Estrogen increases prolactin secretion in late pregnancy to prepare the mammary glands for milk production.

Oxytocin

A small peptide hormone of nine amino acids secreted by the posterior pituitary, synthesized in hypothalamic magnocellular neurons in the supraoptic and paraventricular nuclei.

How is oxytocin released in response to sensory signals?

Nipple suckling and birth canal stretching trigger neural signals that cause oxytocin release from the posterior pituitary into the bloodstream.

Oxytocin Effects

Oxytocin stimulates contraction of smooth muscle in the uterus and mammary glands, causing childbirth contractions and milk ejection, with effects occurring within one minute.

Besides sensory input, what emotional stimuli can trigger oxytocin release in lactating mothers?

Baby crying and skin-to-skin contact activate the hypothalamus, strongly triggering milk ejection via oxytocin release.

What role does oxytocin play during childbirth in the brain?

Increased oxytocin in cerebrospinal fluid helps initiate maternal behavior.

Oxytocin and Corpus Luteum

In some animals, oxytocin from the corpus luteum binds receptors in the endometrium, triggering prostaglandin F2α secretion which causes luteolysis (corpus luteum degeneration).

Prostaglandin F2α (PGF2α)

Also called luteolysin, PGF2α is produced by endometrial glands and causes luteolysis (breakdown of the corpus luteum) in non-pregnant animals.

How does PGF2α reach the ovary from the uterus?

PGF2α moves locally from uterine veins to the ovarian artery via a counter-current transfer mechanism.

Regulation of PGF2α Production

Estradiol increases PGF2α production at the end of the luteal phase, while declining progesterone promotes PGF2α release, triggering luteolysis.

What role do prostaglandins play in ovulation?

Follicular cells produce prostaglandins that help form the ovulatory stigma (rupture site) and assist follicle rupture for ovulation.

Prostaglandins in Childbirth

PGF2α and PGE2 stimulate uterine contractions; they can be administered vaginally or by oxytocin injection to induce labor