MRCOG Part 1 · Endocrinology · Ovarian Function and Disorders

Ovarian Hormones: MRCOG Part 1 questions and key facts

The ovary produces oestrogens, progestogens, and androgens via a coordinated two-cell, two-gonadotrophin system involving thecal and granulosa cells. Oestradiol dominates the follicular phase, driving endometrial proliferation and initiating the mid-cycle gonadotrophin surge. Granulosa cells also produce inhibin, which regulates pituitary follicle-stimulating hormone secretion via negative feedback. Following ovulation, progesterone secreted by the corpus luteum induces secretory transformation and maintains endometrial stability. With luteal regression, the acute withdrawal of progesterone directly precipitates menstruation. After menopause, when ovarian follicular activity ceases, oestrone replaces oestradiol as the predominant circulating oestrogen, derived via peripheral conversion of adrenal and ovarian androgens in adipose tissue.

The Uterio bank has 17 questions on this topic. 2 arebelow in full; the syllabus detail is in the Endocrinology study guide.

How the exam tests Ovarian Hormones

  • Cellular compartmentalisation and enzymatic distribution between thecal and granulosa cells in the two-cell, two-gonadotrophin model of ovarian steroidogenesis.
  • Endocrine timing across the menstrual cycle, including the late follicular oestradiol peak, mid-cycle gonadotrophin surges, and mid-luteal progesterone peak.
  • The direct endocrine trigger of menstruation through luteal regression and subsequent steroid withdrawal, predominantly progesterone.
  • The shift in primary circulating oestrogen from ovarian oestradiol in reproductive years to peripherally synthesised oestrone after the menopause.

High-yield facts

  1. Ovarian thecal cells synthesise androstenedione under luteinising hormone stimulation, which granulosa cells convert to oestrogen under follicle-stimulating hormone stimulation.
  2. Thecal cells lack aromatase activity and are therefore incapable of directly synthesising oestrogens from androgen precursors.
  3. Serum oestradiol peaks in the late follicular phase, shortly before ovulation; sustained high levels switch feedback to positive and trigger the LH surge.
  4. In a typical twenty-eight-day menstrual cycle, the serum oestradiol peak occurs approximately twenty-four to thirty-six hours before the follicle ruptures.
  5. Progesterone levels peak in the mid-luteal phase, approximately seven days after ovulation, corresponding to day twenty-one of a standard twenty-eight-day cycle.
  6. Menstruation is most directly triggered by the rapid withdrawal of progesterone following the regression of the corpus luteum.
  7. Granulosa cells are the principal source of inhibin, which exerts negative feedback on pituitary FSH secretion.
  8. Granulosa cells secrete predominantly inhibin B during the follicular phase, whereas luteinised granulosa cells secrete inhibin A in the luteal phase.
  9. Oestrone is the predominant circulating oestrogen after menopause, formed primarily by peripheral aromatisation of androstenedione in adipose tissue.
  10. Oestradiol is the primary oestrogen during reproductive years, whereas oestriol is produced predominantly by the placenta during pregnancy.

Common pitfalls

  • Assuming granulosa cells make androgens: in the two-cell model thecal cells make androstenedione under LH and granulosa cells aromatise it to oestrogen under FSH.
  • Choosing oestrogen as the trigger for menstruation: both oestrogen and progesterone fall at luteal regression, but progesterone withdrawal is the more direct trigger.
  • Expecting oestradiol to remain the dominant circulating oestrogen after menopause rather than peripherally converted oestrone.

Practice questions: Ovarian Hormones

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Question 1

Endocrinology

Following luteinising hormone (LH) stimulation, which ovarian structure directly contributes to the synthesis of androstenedione, a precursor to oestrogen?

  1. AFollicular granulosa cells
  2. BInterstitial Leydig cells
  3. CAccessory adrenal medullary tissue
  4. DOvarian Sertoli-like cells
  5. EOvarian thecal cells
Show answer and explanation

Correct answer: E. Ovarian thecal cells

Key takeaway

Ovarian thecal cells directly synthesise androstenedione in response to luteinising hormone (LH) stimulation, providing the precursor for oestrogen production.

Luteinising hormone (LH) primarily targets ovarian thecal cells to stimulate the production of androstenedione.

During the follicular phase of the ovarian cycle, LH binds to receptors on the thecal cells, triggering a cascade that activates enzymes involved in steroidogenesis. The primary product of this LH stimulation is androstenedione, which is then converted into oestradiol. This process of converting androstenedione into oestradiol is carried out by granulosa cells.

Granulosa cells, while crucial in oestrogen synthesis, primarily convert androstenedione (produced by the thecal cells) into oestrogen under the influence of Follicle-stimulating hormone (FSH). They do not directly synthesise androstenedione in response to LH.

Interstitial Leydig cells are the androgen-secreting cells of the testis; the ovary's only Leydig-like cells are the small hilus cells, which make a minor contribution to circulating androgen and do not supply the follicle with its oestrogen precursor. Accessory adrenal medullary tissue would secrete catecholamines, not steroids, because the adrenal medulla is derived from neural crest and lacks the steroidogenic pathway of the cortex. Ovarian Sertoli-like cells are not a normal ovarian cell population: Sertoli cells are testicular supporting cells, and Sertoli-like elements appear in the ovary only in rare sex cord–stromal tumours.

Question 2

Endocrinology

Which ovarian cell type is primarily responsible for the production of inhibin?

  1. ATheca interna cells
  2. BGranulosa cells
  3. CCorpus luteum cells
  4. DInterstitial cells
  5. ECumulus cells
Show answer and explanation

Correct answer: B. Granulosa cells

Key takeaway

Granulosa cells in the ovarian follicles are the principal producers of inhibin, which plays a crucial role in the negative feedback regulation of follicle-stimulating hormone (FSH) secretion.

Inhibin is a glycoprotein hormone of the ovarian follicle that acts on the anterior pituitary to suppress follicle-stimulating hormone (FSH) secretion selectively, with little effect on LH. It is produced by the granulosa cells, which line the follicle inside its basement membrane and express the inhibin α- and β-subunit genes. Granulosa cells of small growing follicles secrete mainly inhibin B during the follicular phase; after ovulation the same cell lineage, now luteinised, secretes mainly inhibin A, which peaks in the mid-luteal phase.

Theca interna cells lie outside the basement membrane and, under LH stimulation, produce androgens (mainly androstenedione) that pass to the granulosa cells for conversion to oestrogen; they do not produce inhibin. Corpus luteum cells do secrete inhibin A, but only because the granulosa-lutein cells of the corpus luteum are derived from the granulosa cells of the ruptured follicle; the theca-lutein cells make androgens and progesterone, so the cell type responsible for inhibin is the granulosa lineage. Interstitial cells of the ovarian stroma are steroidogenic cells that contribute androgens, particularly after the menopause. Cumulus cells are a specialised subset of granulosa cells that surround the oocyte and support its maturation through gap-junction coupling; their recognised role is oocyte support through gap-junction coupling, so they are not the cell type named as the source of inhibin.

15 more ovarian hormones questions in the bank

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What the syllabus covers under ovarian hormones

  • Oestrogen
  • Progesterone
  • Androgens

Read the full section in the Endocrinology guide, or check the next exam dates.