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Questions and Answers
What is the primary role of Follicular-Stimulating hormone (FSH) in the reproductive system?
What is the primary role of Follicular-Stimulating hormone (FSH) in the reproductive system?
What hormone peaks after ovulation during the menstrual cycle?
What hormone peaks after ovulation during the menstrual cycle?
Which hormones are classified as gonadotropins?
Which hormones are classified as gonadotropins?
Which hormone functions as a negative feedback factor for FSH release from the pituitary?
Which hormone functions as a negative feedback factor for FSH release from the pituitary?
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Which substance serves as a precursor in the biosynthesis of sex hormones?
Which substance serves as a precursor in the biosynthesis of sex hormones?
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What defines infertility in a couple?
What defines infertility in a couple?
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Which test indicates whether ovulation has occurred in women?
Which test indicates whether ovulation has occurred in women?
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Which serum FSH level indicates primary gonadal failure in both men and women?
Which serum FSH level indicates primary gonadal failure in both men and women?
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What should be included in the clinical history taking for infertility investigations?
What should be included in the clinical history taking for infertility investigations?
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Which physical examination finding could indicate hyperprolactinaemia?
Which physical examination finding could indicate hyperprolactinaemia?
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Which condition is NOT commonly associated with female infertility?
Which condition is NOT commonly associated with female infertility?
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Which of the following is a possible indication of oligomenorrhoea during the investigation of female infertility?
Which of the following is a possible indication of oligomenorrhoea during the investigation of female infertility?
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What is the common clinical history factor to assess in both male and female infertility investigations?
What is the common clinical history factor to assess in both male and female infertility investigations?
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Study Notes
Genital (Reproductive) System
- The genital system, also known as the reproductive system, is controlled by the anterior lobe of the pituitary gland.
- Sex hormones, or sex steroids, are a group of steroids synthesized in the testes, ovaries, adrenal glands, and placenta during pregnancy.
- Gonads are the organs that produce gametes.
- In males, the gonads are the testes; in females, the ovaries.
- Gametes (e.g., spermatozoa and egg cells) are haploid germ cells.
Gonads
- Gonads produce steroid hormones.
- Sex steroids regulate the maturation of sex organs and secondary sexual characteristics.
- Sex steroid control is influenced by LH and FSH.
- LH and FSH are controlled by hypothalamic GnRH.
Follicular-Stimulating Hormone (FSH) and Luteinizing Hormone (LH)
- FSH and LH are gonadotropins, secreted by gonadotrophs which synthesize and secrete both.
- Both are peptide hormones.
- Secretion of gonadotropins is mainly under positive control.
- GnRH from the hypothalamus stimulates gonadotrophs to secrete both LH and FSH.
Functions of LH and FSH
- LH and FSH stimulate the gonads to secrete sex steroids, like estrogen in women and testosterone in men.
- FSH stimulates gonadal release of inhibin, which acts as negative feedback to block FSH release by the pituitary.
- LH and FSH stimulate gonadal release of activin, which has positive feedback on gonadotropin secretion.
- Gonadal sex steroid secretions (estrogen and testosterone) exert negative feedback on the hypothalamus, reducing GnRH secretion, and directly on gonadotrophs, reducing gonadotropin secretion.
Female HPG Axis
- This is the hypothalamic-pituitary-gonadal axis in females.
- The hypothalamus secretes GnRH, which stimulates the anterior pituitary to release LH and FSH.
- LH and FSH act on the ovaries, stimulating estrogen and progesterone production.
- Progesterone and estrogen in turn influence the hypothalamus, effectively regulating hormone levels.
Hormones (Classified by Chemical Structure)
- Hormones are classified by their chemical structure.
- Lipid derivatives (e.g., eicosanoids) are derived from arachidonic acid. (including leukotrienes, prostaglandins, thromboxanes, and prostacyclins).
- Steroid hormones are structurally related to cholesterol.
- Gonads produce androgens (e.g., testosterone), estrogens (e.g., estradiol, estrone, estriol), and progestins.
- Adrenal cortex produces mineralocorticoids, glucocorticoids, and androgens.
- Kidneys produce calcitriol.
Androgen (Testosterone)
- Testosterone is the most important natural androgen.
- It's primarily synthesized by interstitial cells in the testes and, in smaller amounts, by the ovaries and adrenal cortex.
- Adult male testosterone secretion is regulated by hormonal signals from the hypothalamus, via pituitary release of LH and FSH.
- Natural androgens include testosterone, dihydrotestosterone, dehydroepiandrosterone, androstenedione, and androsterone
Estrogens
- Naturally occurring estrogens in humans include estradiol, estrone, and estriol.
- Estradiol is the primary circulating and most active estrogen.
- Estriol is prominent in late pregnancy.
- Estrone is found in the urine of pregnant women and placenta.
- All estrogens share a characteristic aromatic ring structure with three double bonds, lack a methyl group at C10, and have a core structure of C18.
Sex Hormones Metabolism
- Cholesterol is a precursor to all steroid hormones.
- Steroid hormone synthesis occurs in the mitochondria and smooth endoplasmic reticulum.
- Cholesterol is converted to pregnenolone in the mitochondria via a cytochrome P450 side-chain cleavage enzyme (P450scc) or desmolase.
- Removing the side chain in pregnenolone creates the 21-carbon steroid.
Steroid Hormone Biosynthesis
- Steroid hormones arise from cholesterol via pregnenolone.
- Cholesterol is converted into pregnenolone within mitochondria by a specific transport protein.
- Within the Inner mitochondrial membrane, enzymes (Cytochrome P450 side chain-cleavage enzyme (P450scc)) complete the cholesterol to pregnenolone conversion.
- Steroid hormone biosynthesis is the process of creating steroid hormones from cholesterol.
Metabolites of Estrogen
- Estradiol and estrone can be interconverted.
- Estradiol and estrone are metabolized in the liver into various metabolites, including estriol.
Mechanism of Action
- Testosterone enters target cells and is converted to DHT.
- Activated hormones then bind to intracellular hormone-response elements (HREs) to control gene transcription and protein synthesis.
- Estrogen acts similarly, with ER-α and ER-β as its receptor.
Menstrual Cycle
- The menstrual cycle involves fluctuations in estrogen and progesterone levels.
- During the follicular phase, estrogen levels rise due to developing follicles. Progesterone isn't made.
- Ovulation occurs when estrogen levels drop and follicles rupture.
- The luteal phase features rising progesterone from the corpus luteum, along with increasing estrogen.
- Menstruation happens when the corpus luteum degrades, causing estrogen and progesterone levels to decline.
Ovarian Hormone Levels
- Shows graph trends for Estrogen and Progesterone during menstrual cycle.
- Estrogen rises throughout the follicular phase.
- Estrogen levels decrease at the time of ovulation.
- Progesterone rises consistently in the luteal phase and levels fall shortly after ovulation with the decline of the corpus luteum.
Investigations of Infertility
- Infertility is the failure of a couple to conceive after one year of regular unprotected intercourse.
- Factors causing infertility include endocrine problems, typically more common in women than men. Elevated progesterone levels at day 21 in women indicates occurring ovulation.
- For both men and women, elevated FSH (>25U/L) suggests primary gonadal failure.
Clinical History Taking for Infertility
- Complete medical history including previous pregnancies, contraceptive use, past illnesses, chemotherapy or radiotherapy, abnormalities, smoking, drug use, and frequency of intercourse is essential.
Physical Examination for Infertility
- Physical exams should assess for indications of hypothalamic-pituitary or thyroid disorders, Cushing's syndrome, galactorrhea (unrelated to pregnancy), or hirsutism (excess hair growth).
Investigation of Female Infertility
- A diagram shows a diagnostic approach to female infertility.
- Determining if ovulation is occurring during the menstrual cycle (via checking progesterone levels) is critical.
- A range of investigations are needed including ovarian reserve and function assessments.
- Measuring LH, FSH, and prolactin levels helps determine if there are any problems in the HPG pathway.
Endocrine Causes of Infertility in Women
- Ovarian androgen secretion is problematic in women, especially tied to conditions like obesity and insulin resistance.
- Primary ovarian failure, postmenopausal hormonal pattern, or low/absent levels of oestradiol are all potential culprits.
- Hormone replacement therapy can address some symptoms but is not a cure.
Diagnosis of PCOS
- Diagnosis requires at least two of three criteria: oligo-ovulation or anovulation, hyperandrogenism (clinical or biochemical signs of excess androgens), and polycystic ovaries on ultrasound.
Investigation of Male Infertility
- A flowchart presents a diagnostic approach to male infertility, involving history & clinical examination, sperm analysis, and hormone checks (testosterone and gonadotropins, & Prolactin).
- Primary testicular failure involves both interstitial cell and testicular tubule damage.
- Damage to interstitial cells causes suppressed testosterone.
- Tubule damage can lead to selective FSH increases while testosterone levels remain normal
Semen Analysis
- Semen analysis is performed to assess semen volume, liquefaction time, sperm density, motility, presence of abnormal sperm (morphology or motility issues).
- Semen analysis also evaluates pH and WBC content.
Spermatogenesis Metabolism
- A diagram displays the process—a branched pathway—for spermatogenesis, involving the progressive divisions (mitosis and meiosis) of spermatogonia, into primary spermatocytes, secondary spermatocytes, spermatids, and finally sperm.
Primary Testicular Failure
- Damage to both interstitial cells and tubules leads to decreased testosterone and elevated gonadotropins (LH and FSH).
- Tubular impairment alone can result in increased FSH without affecting androgen levels.
Hyperprolactinemia
- Prolactin is an anterior pituitary hormone whose secretion is controlled by signals from the hypothalamus.
- TRH stimulates and dopamine inhibits prolactin release.
- Prolactin acts directly on the mammary glands to stimulate lactation.
- Hyperprolactinemia is characterized by increased prolactin levels with potentially fertility-damaging effects on the gonads.
- Common causes include drug use, stress, primary hypothyroidism, or pituitary disorders such as prolactinomas.
Investigation of Amenorrhea
- A systematic approach involves a detailed history, physical exam, hormone testing (estrogen, FSH, LH), thyroid function tests, karyotyping, bone age assessment, and prolactin measurement.
- Other tests include testosterone, DHEAS, 17-OH Prog, androstenedione assessments.
- Imaging (pelvic ultrasound) is used to identify underlying causes, including chronic illnesses.
Causes of Amenorrhea
- Amenorrhea can be due to various factors, including chromosomal abnormalities, physiological delays, Mullerian agenesis, imperforate hymen, hypothalamic issues, and others.
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Description
Explore the key components of the genital (reproductive) system, including the roles of gonads, sex hormones, and important hormone controls like FSH and LH. This quiz emphasizes the synthesis and functions of sex steroids and the hormonal regulation by the pituitary gland and hypothalamus.
