Reproduction

BCH 120 — Metabolic & Endocrine Biochemistry · Dr. Radi

build Jul 17 · 11:11 · CC BY-NC-SA 4.0 · owned figures (RDKit / matplotlib / PyMOL)
Dr. Radi

By the end of this unit, you can…

  • Explain sex-steroid synthesis (cholesterol → testosterone via StAR/LH; 5α-reductase → DHT; aromatase → estradiol) and the hypothalamic–pituitary–testis axis, testis structure, and kisspeptin
  • Describe sex differentiation (SRY/AMH/testosterone; female default) and its disorders (CAH, 5α-reductase deficiency, androgen insensitivity), plus puberty and its timing disorders
  • Explain ovarian estrogen synthesis (two-cell model), the hypothalamic–pituitary–ovarian axis with its estrogen positive-feedback LH surge, the menstrual cycle, and common disorders
  • Describe pregnancy — hCG's rescue of the corpus luteum, the placenta's hormones (progesterone, hPL, relaxin, estrogen), miscarriage, and parturition (oxytocin positive feedback, prostaglandins, labor) and contraception
  • Explain twins (mono- vs dizygotic), IVF, and lactation (prolactin/oxytocin, lactose synthesis, colostrum vs milk)
Dr. Radi

Today's route 🗺️

  1. Sex Steroid Synthesis
  2. The HPG Axis & the Testis
  3. Sex Differentiation & Puberty
  4. The Ovary, Estrogen & the HPO Axis
  5. The Menstrual Cycle
  6. Pregnancy, hCG & the Placenta
  7. Parturition, Labor & Contraception
  8. Twins, IVF & Lactation
Dr. Radi

1 · Sex Steroid Synthesis

"The sex hormones — testosterone, DHT, estradiol — all come from the same cholesterol pathway you learned for the adrenal cortex. Three enzymes decide the outcome: StAR gates the whole thing, 5α-reductase sharpens the androgen, and aromatase turns androgens into estrogens."

Dr. Radi

Meet the sex steroids

Here are the three you must know, and they're all four-ring steroids — cousins of cortisol from last unit. Testosterone is the main androgen. DHT (dihydrotestosterone) is testosterone with one extra reduction — and it's the more potent androgen (it binds the receptor harder and can't be aromatized away). Estradiol is the main estrogen — notice its aromatic A-ring, the tell-tale of an estrogen. Small edits to one skeleton, three very different signals.

Dr. Radi

One backbone, three fates

The synthesis is the adrenal pathway again: cholesterol → pregnenolone → … → testosterone, with the rate-limiting step being StAR ferrying cholesterol into the mitochondrion — driven here by LH (the same StAR that ACTH controls in the adrenal). Then testosterone branches. 5α-reductase converts it to DHT — amplifying the androgen signal in target tissues. Or aromatase (a P450) converts the C19 androgen into the C18 estrogen, estradiol. One enzyme choice flips "male" to "female" signal.

Dr. Radi

2 · The HPG Axis & the Testis

"Male reproduction runs on the same three-tier axis as every gland in this course — hypothalamus, pituitary, testis — with a molecular gatekeeper (kisspeptin) that decides when puberty begins. And inside the testis, two cell types split the work."

Dr. Radi

The hypothalamic–pituitary–testis axis

Same three-tier logic, one new gatekeeper. The hypothalamus releases GnRH — but only when kisspeptin (from KNDy neurons) gives the go-ahead, which is what flips on at puberty. GnRH drives the pituitary to release LH and FSH. LH hits Leydig cells → testosterone; FSH hits Sertoli cells → sperm + inhibin B. Then feedback: testosterone inhibits GnRH/LH, and inhibin inhibits FSH. All negative — so testosterone runs at a steady, "tonic" level (unlike the cyclic female).

Dr. Radi

Inside the testis

The testis divides its labor between two cell types. The seminiferous tubules (80% of the volume) house the Sertoli cells, which nurse developing sperm — and their tight junctions form the blood-testis barrier, walling sperm off from the immune system. Between the tubules sit the Leydig cells, which make testosterone on LH's command. One structural quirk worth knowing: the testes hang outside the body in the scrotum (~33 °C) because spermatogenesis needs the cooler temperature — undescended testes (cryptorchidism) impair it.

Dr. Radi

3 · Sex Differentiation & Puberty

"Every embryo starts the same — bipotential gonads and both duct systems — and the default path is female. One gene (SRY) and two hormones (AMH, testosterone) build the male. When they misfire, you get the disorders of sex development; and kisspeptin decides when puberty begins."

Dr. Radi

The default is female

Here's the elegant developmental logic. Every fetus begins with a bipotential gonad and both duct systems (Müllerian and Wolffian). The male path needs an active push: the SRY gene on the Y chromosome (via SOX9) turns the gonad into a testis, whose Sertoli cells make AMH (regressing the Müllerian ducts) and whose Leydig cells make testosterone (building the Wolffian ducts into the vas deferens). Without SRY — the default — the gonad becomes an ovary, Wolffian ducts regress, and the Müllerian ducts become the uterus and tubes. Female unless told otherwise.

Dr. Radi

When it varies — DSD and puberty

Break a step and you get a disorder of sex development. CAH (an enzyme block) shunts precursors into androgens, masculinizing a female fetus. 5α-reductase deficiency (no DHT) leaves a male under-virilized at birth. An androgen-receptor defect gives complete androgen insensitivity — a genetic male with a female phenotype because tissues can't hear testosterone. And timing itself is controlled: kisspeptin reawakens GnRH pulses to start puberty — too early is precocious, too late is delayed puberty (a hypothalamic, pituitary, or gonadal fault).

Dr. Radi

4 · The Ovary, Estrogen & the HPO Axis

"The ovary makes estrogen through a two-cell team that neither cell could run alone. And its axis has a twist found nowhere else in the body: estrogen's feedback flips from negative to positive to trigger ovulation."

Dr. Radi

The two-cell model of estrogen

Estrogen synthesis in the ovarian follicle takes two cells working together. The theca cell, under LH, converts cholesterol to an androgen (androstenedione) — but it can't finish the job. It hands that androgen to the neighboring granulosa cell, which, under FSH, uses aromatase to turn it into estradiol. Neither cell can make estrogen alone: theca makes the androgen, granulosa aromatizes it. This division of labor is why both LH and FSH are needed to grow a follicle.

Dr. Radi

The HPO axis — feedback that flips

The hypothalamic-pituitary-ovarian axis starts like all the others: GnRH → LH/FSH → ovarian estradiol + progesterone, with estradiol normally feeding back negatively. But here's the twist that makes females cyclic rather than tonic: when a dominant follicle pumps out sustained high estradiol at mid-cycle, the feedback flips to positive — triggering a massive LH surge that causes ovulation. The follicle literally times its own release by how much estrogen it makes. No other axis in the body does this.

Dr. Radi

5 · The Menstrual Cycle

"The menstrual cycle is a monthly hormonal relay with one goal: release a mature egg and prepare the uterus for it. Learn the four hormone curves and the two phases, and the whole thing — including what goes wrong — falls into place."

Dr. Radi

The cycle in four hormones

Read the ~28-day cycle as two phases split by ovulation. In the follicular phase, FSH grows a follicle, which makes rising estradiol (building the uterine lining). When estradiol peaks, its positive feedback fires the mid-cycle LH surge → ovulation (day ~14). In the luteal phase, the leftover follicle becomes the corpus luteum, pouring out progesterone to hold the lining ready. If no pregnancy, the corpus luteum dies, progesterone falls, and the lining sheds — menstruation — restarting the cycle.

Dr. Radi

When the cycle goes wrong

Because the cycle is a tightly timed hormone relay, a lot can perturb it. PCOS (polycystic ovary syndrome) — androgen excess blocks ovulation, causing cysts, irregular cycles, and insulin resistance. Amenorrhea — no periods at all, often from stress or low body fat shutting down GnRH. Endometriosis — uterine lining grows outside the uterus, causing pain and infertility. Dysmenorrhea — painful periods driven by prostaglandin cramps (which is why NSAIDs help). Common, and all traceable to the hormones you just mapped.

Dr. Radi

6 · Pregnancy, hCG & the Placenta

"Pregnancy hijacks the cycle to keep it from ending. A single hormone from the new embryo — hCG — rescues the corpus luteum so progesterone keeps flowing. Then the placenta takes over as a temporary endocrine organ running the whole show."

Dr. Radi

hCG rescues the pregnancy

Normally, if there's no pregnancy, the corpus luteum dies, progesterone falls, and the lining sheds. Pregnancy has to prevent that — and the trick is hCG. As soon as the embryo implants, its placenta makes human chorionic gonadotropin (hCG), which acts like LH to keep the corpus luteum alive, so it keeps making progesterone and the uterine lining holds. hCG peaks around week 10, then fades as the placenta makes its own progesterone. And it's exactly what a pregnancy test detects — the earliest hormonal sign.

Dr. Radi

The placenta as an endocrine organ

Once established, the placenta runs pregnancy hormonally. hCG carries the early rescue. Progesterone keeps the uterus quiet (no contractions) and the pregnancy secure. Human placental lactogen (hPL) re-tunes the mother's metabolism to shunt fuel to the fetus (a bit like GH, and mildly diabetogenic). Relaxin and estrogen loosen the pelvis and grow the uterus and breasts for delivery and feeding. A whole temporary gland — and when it or the corpus luteum fails early, the result can be miscarriage.

Dr. Radi

7 · Parturition, Labor & Contraception

"Birth is powered by one of the body's rare positive-feedback loops — the only place we celebrate a runaway cycle. And contraception works mostly by turning the female axis's own negative feedback against ovulation."

Dr. Radi

Birth: a rare positive-feedback loop

Almost every loop in this course is negative (self-limiting). Labor is the dramatic exception. As the baby's head stretches the cervix, the posterior pituitary releases oxytocin, which drives uterine contractions, which push the baby down and stretch the cervix more — releasing still more oxytocin. It amplifies instead of settling, building until delivery finally breaks the loop. Prostaglandins help by ripening the cervix and boosting contractions. The result is the three stages of labor: dilation, delivery of the baby, then delivery of the placenta.

Dr. Radi

Contraception — hijacking the feedback

Most contraception is just clever endocrinology. Hormonal methods give steady estrogen + progestin, which — through the negative feedback you learned — suppress LH and FSH so no follicle matures and no ovulation happens; as backup, they thicken cervical mucus and thin the endometrium. Non-hormonal methods work mechanically instead — barrier methods (condoms), the copper IUD, or sterilization — blocking sperm or fertilization without touching the hormone axis. Same goal, two very different levers.

Dr. Radi

8 · Twins, IVF & Lactation

"Finish the course where life does: two babies from one egg (or two), a lab that borrows the whole HPO axis to make pregnancy happen, and the two-hormone system — prolactin and oxytocin — that feeds the newborn."

Dr. Radi

Twins and IVF

Two ways to get twins, and they're genetically opposite. Monozygotic ("identical") twins come from one fertilized egg that splits — same DNA. Dizygotic ("fraternal") twins come from two eggs fertilized by two sperm — just siblings who shared a womb. And when nature needs help, IVF (in vitro fertilization) borrows the whole axis on purpose: high-dose FSH forces many follicles to mature at once, an LH-like trigger finishes them, the eggs are retrieved, fertilized in the lab, and an embryo is transferred back. The endocrinology of the cycle, run deliberately.

Dr. Radi

Lactation — the baby runs the supply

Feeding the newborn takes two hormones. Prolactin drives milk synthesis — including lactose, built by lactose synthase (galactosyltransferase + α-lactalbumin, the classic intro-biochem example). Oxytocin drives the "let-down" reflex, contracting the gland to eject milk. Both are triggered by suckling: nursing lifts the dopamine brake on prolactin and fires oxytocin, so the infant controls the supply. First comes colostrum — low in fat and volume but packed with protective antibodies (IgA) — then energy-dense mature milk; the baby's growth is then tracked on percentile charts against peers. And that's the endocrine journey, birth to first meal.

Dr. Radi

Can you…?

  • ☐ explain sex-steroid synthesis (cholesterol → testosterone via StAR/LH; 5α-reductase → DHT; aromatase → estradiol) and the hypothalamic–pituitary–testis axis, testis structure, and kisspeptin?
  • ☐ describe sex differentiation (SRY/AMH/testosterone; female default) and its disorders (CAH, 5α-reductase deficiency, androgen insensitivity), plus puberty and its timing disorders?
  • ☐ explain ovarian estrogen synthesis (two-cell model), the hypothalamic–pituitary–ovarian axis with its estrogen positive-feedback LH surge, the menstrual cycle, and common disorders?
  • ☐ describe pregnancy — hCG's rescue of the corpus luteum, the placenta's hormones (progesterone, hPL, relaxin, estrogen), miscarriage, and parturition (oxytocin positive feedback, prostaglandins, labor) and contraception?
  • ☐ explain twins (mono- vs dizygotic), IVF, and lactation (prolactin/oxytocin, lactose synthesis, colostrum vs milk)?

If any box stays empty, the practice site has a drill for it. 🧪

Dr. Radi