PHAR300: Estrogens & Progestins: Contraceptive and Other Uses

Vocabulary practice flashcards covering the HPG axis, ovarian steroidogenesis, hormonal actions, steroid receptor biology, hormonal contraception, emergency contraception, and contragestation based on PHAR300 lecture materials.

Estrogens

A class of steroid hormones consisting of 18 carbons (including estrone [$E_1$], estradiol [$E_2$], and estriol [$E_3$]), rather than a single distinct molecule.

Progestogens

A class of 21-carbon steroid molecules naturally produced endogenously within the body, including progesterone ($P_4$) and $17\alpha$-hydroxyprogesterone.

Progestins

Synthetic pharmaceutical drugs engineered to exert progesterone-like biological activities that are not produced endogenously in the body.

Receptor Subtypes

Receptor proteins that are products of distinct, different genes, such as $ER\alpha$ (encoded by $ESR1$) and $ER\beta$ (encoded by $ESR2$).

Receptor Isoforms

Different protein variants transcribed from the same gene via alternative promoters or alternative splicing, such as $PR\text{-}A$ and $PR\text{-}B$.

Gonadotropin-releasing hormone (GnRH)

A small pulsatile peptide synthesized in the hypothalamus and released into the pituitary portal system to stimulate the synthesis and secretion of FSH and LH via a GPCR.

Follicle-stimulating hormone (FSH)

An anterior pituitary gonadotropin that drives ovarian follicle recruitment, dominant follicle selection, and aromatase ($CYP19$) expression in granulosa cells.

Luteinizing hormone (LH)

An anterior pituitary gonadotropin that stimulates theca cells to synthesize androgens and whose mid-cycle surge triggers ovulation and corpus luteum formation.

Granulosa cells

Inner ovarian somatic cells adjacent to the oocyte that respond to FSH; they contain aromatase to produce estrogens but lack the enzymes required to synthesize androgens.

Theca cells

Outer somatic cells of the ovarian follicle that express LH receptors and synthesize androgens (androstenedione and testosterone) from cholesterol precursors.

Two-cell / two-gonadotropin model

The collaborative ovarian pathway where LH stimulates theca cells to synthesize androgens, which subsequently diffuse into granulosa cells where FSH-stimulated aromatase converts them into estrogens.

Aromatase (CYP19)

A cytochrome P450 enzyme in granulosa cells that catalyzes the conversion of 19-carbon androgens into 18-carbon estrogens (androstenedione to estrone; testosterone to estradiol).

$17\beta$-Estradiol ($E_2$)

The most potent endogenous estrogen; it drives endometrial proliferation, acts as a mitogen, and at high concentrations triggers the ovulatory LH surge through positive feedback.

Corpus luteum

An endocrine structure formed from luteinized granulosa and theca cells post-ovulation that secretes high amounts of progesterone and estradiol with a lifespan of approximately $2\text{ weeks}$ in the absence of pregnancy.

Human chorionic gonadotropin (hCG)

A hormone produced by the blastocyst and syncytiotrophoblast that binds to LH receptors on the corpus luteum, rescuing it from luteolysis to maintain progesterone secretion during early gestation.

Sex hormone-binding globulin (SHBG)

A hepatic plasma glycoprotein that binds circulating lipophilic steroids with high affinity, whose synthesis is elevated by estrogen exposure.

Hormone response element (HRE)

A specific DNA regulatory sequence (e.g., ERE) recognized and bound by ligand-activated, dimerized nuclear steroid receptors and recruited coregulators to modulate gene transcription.

Ethinyl estradiol (EE)

A synthetic estrogen containing a $C17$ ethinyl group that impedes hepatic first-pass metabolism, elevating oral bioavailability from approximately $5\%$ to greater than $40\%$.

Conjugated equine estrogens (Premarin)

An estrogen mixture obtained from pregnant mare urine utilized predominantly as hormone replacement therapy in postmenopausal women.

Selective estrogen receptor modulators (SERMs)

Non-steroidal estrogen receptor ligands (e.g., clomiphene, raloxifene, tamoxifen) that exhibit tissue-selective agonist or antagonist activity based on tissue-specific coregulator expression.

Selective estrogen receptor degrader (SERD)

A class of antiestrogens (e.g., fulvestrant) that binds directly to estrogen receptors, prompting their down-regulation and proteasomal degradation.

Combined oral contraceptive (COC)

A hormonal regimen containing an estrogen and a progestin that prevents pregnancy primarily by providing continuous negative feedback on the HPG axis, abolishing the LH surge and ovulation.

Enterohepatic circulation

The recycling pathway where conjugated steroids excreted into bile are hydrolyzed by intestinal microflora $(\beta\text{-glucuronidases})$ back into free lipophilic steroids for reabsorption, which is susceptible to disruption by broad-spectrum antibiotics.

Venous thromboembolism (VTE)

A serious adverse effect associated with combined oral contraceptives, caused by estrogen-induced increases in hepatic clotting factors (VII to X) and suppression of antithrombin III.

Progestin-only pill (mini-pill)

An oral contraceptive devoid of estrogen that acts primarily by thickening cervical mucus and promoting endometrial atrophy, serving as an alternative for patients at risk for thromboembolism.

Ulipristal acetate

A selective progesterone receptor modulator (SPRM) with mixed agonist/antagonist activity used for emergency contraception within $120\text{ hours}$ ($5\text{ days}$) of intercourse by inhibiting or delaying ovulation.

Mifepristone (RU-486)

A competitive antagonist at progesterone and glucocorticoid receptors with a 5-fold higher affinity for PR than endogenous progesterone, used clinically for contragestation.

Misoprostol (Cytotec)

A synthetic prostaglandin $E_1$ ($PGE_1$) analogue that stimulates $G_q$-coupled prostanoid receptors to raise intracellular $\text{Ca}^{2+}$, producing myometrial contractions and cervical expulsion.

Contragestation

The pharmacological termination of an established, ongoing pregnancy (medical abortion), distinct from contraception which acts to prevent pregnancy.