L7 Endocrine Physiology of the Testes Flashcards
Endocrine Hromones of the Testes?
Testosterone (androgen)
- spermatogenesis
- sexual maturation (puberty)
- sexual differentiation (masculinization of reproductive tract
and external genitalia)
Inhibin: -ve feedback regulation of FSH (gonadotropin)
Anti-müllerian hormone (AMA): sexual differentiation
________ produce a number of hormones including AMH (anti mullerian hormone) and Inhibin. They are the Target for FSH
Sertoli Cells produce a number of hormones including AMH (anti mullerian hormone) and Inhibin. They are the Target for FSH
__________ released by neuroendocrine cells in arcuate nucleus of the hypothalamus stimulates LH and FSH secretion by gonadotroph cells of the ____________________.
- LH acts on _________
- FSH acts on ________
Importance/Regulation?
GnRH released by neuroendocrine cells in arcuate nucleus of the hypothalamus stimulates LH and FSH secretion by gonadotroph cells of the anterior pituitary.
- LH acts on Leydig cells (Testosterone Production)
- FSH acts on Sertoli cells (Inhibin/AMH Production)
Both are necessary for normal fertility and reproduction!!
Regulation
- negative feedback by testosterone /inhibin
- stress
Master hormone controlling fertility and reproduction?
What is Essential for it’s Function?
GnRH
Produced in a pulsatile manner by neuroendocrine cells found in the pre-optic region and arcuate nucleus of the hypothalamus (ESSENTIAL FOR NORMAL LH/FSH SECRETION)
Key Ensymes involved in Sex Steroid Synthesis?
5-10% testosterone converted to more potent androgen dihydrotestosterone by 5- Alpha reductase
Aromatase converts androgens to estradiol
Testosterone vs. Dihydrotestosterone (DHT)
Testosterone and DHT have overlapping but distinct
functions
- DHT formed from testosterone by 5-alpha reductase
- DHT is a more potent androgen
In sexual differentiation:
- Testosterone responsible for the development of internal reproductive tissues (epididymis, seminal vesicles and vas deferens)
- DHT responsible for the development of male external genitalia and prostate
Pathogenesis of Male Pattern Baldness?
In adult males, 5- alpha reductase is highly expressed in prostate and hair follicles (Converts Testoreone => DHT):
- male pattern baldness=> inhibiting restores hair
- benign prostatic hyperplasia (BPH)
Hormonal mediation of phenotypic sex?
MIS/AMH => regression of Mullerian Duct
Testoerone=> Wolfian Duct transformation to Epididymis, Vas Deferens, Seminal Vessicles, Ejaculatory Duct
Dihydrotestosterone => development of Penis, Scrotum, Prostate
Manifestation of Andropause (Androgen Deficiency Aging Male -ADAM)
Incidence/Causes of Male Infertility
Cause/Manifestation of Primary Hypogonadism ‘Hypergondadotropic hypogonadism’
Gonads not producing enough testosterone despite increases in FSH and LH
Impaired gonadotrophin responsiveness:
- FSH and LH receptor mutations
Defective androgen synthesis
* 5a-reductase deficiency
LOW Testosterone w/ HIGH levels of gonadotropins
- LOW testosterone/ DHT
- HIGH LH/FSH
Cause/Manifestations of 5-Alpha Reductase Deficiency?
Autosomal recessive disorder affecting males (DHT absence) leading to phenotypic heterogeneity
Characteristics
- male gonads have high-frequency cryptorchidism (fail to descend)
- microphallus, ambiguous or female genitalia (macroclitoris, pseudovagina)
- amenorrhea and virilisation at puberty in girls
- males may be fertile/subfertile/infertile often with oligospermia (Low Sperm) or azoospermia (No Sperm)
Cause/Manifestations of Secondary Hypogonadism
‘Hypogonadotropic Hypogonadism’
Reduction in both testosterone and gonadotropin (FSH/LH) levels
GnRH insufficiency
Hypopituitarism (tumours, surgical trauma, andropause)
Isolated LH or FSH deficiency
Hyperprolactinemia
Congenital adrenal hyperplasia
Cushings syndrome
Cause/Manifestations of Kallman Syndrome?
Inherited disorder of deficient GnRH production
- Mutations in KAL1 gene interfere with migration of GnRH secreting neurons to hypothalamus during development
- Characterised by hypogonadotrophic hypogonadism (HH), infertility and absent/incomplete/partial pubertal maturation (LOW FSH, LOW LH, Delayed/absenct puberty)
- 50% of cases have anosmia or hyposmia (lack of/reduced sense of smell) – distinguishes Kallman syndrome from other HH syndromes
Hypogonadotropic Hypogonadism associated with anosmia or hyposmia (lack of/reduced sense of smell)?
Kallman Syndrome
- Inherited disorder of deficient GnRH production
- Mutations in KAL1 gene interfere with migration of GnRH secreting neurons to hypothalamus during development
Causes/Manifestation of Hyperprolactinemia?
Causes
- 40% of all cases due to benign (functioning) pituitary adenomas (prolactinomas)
- Other pituitary tumours or pathologies that lower dopamine levels in the hypophyseal portal system (Decrease in Dopamine (Inhibitor) => Hyperprolactienetma)
Manifestations
- Hyperprolactinemia stimulates lactation (milk production) and interferes with gonadal function (hypogonadism) by suppressing LH and FSH secretion
- Males: infertility and loss of libido is most common
- Females: Galactorrhea (Nipple Discharge), Amenorrhea
Cause/Manifestations of Insensitivity Syndrome?
X linked recessive inheritance => inactivating mutations in androgen receptor
Appear female, have testes, no uterus, no ovaries, external genitalia of female
Cause/Manifestation of Cushing’s Disease?
Secondary Hypercortisolism due to either pituitary or extrapituitary ACTH excess
Cause:
- Adrenocorticotropic Hormone (ACTH) stimulates cortisol production AND adrenal androgen production (DHEA)
- Increased negative feedback regulation by adrenal androgens in hypothalamus and pituitary reduces LH and FSH production
Manifestation
- Amenorrhea in females
- Sub/infertility in males
Production/Role/Regulation of Adrenal Androgens?
Adrenal cortex produces primarily androgens (male sex hormones)
DHEA is the most abundant circulating androgen
- DHEA weak androgen but can be converted to much more potent testosterone
- DHEA plays role in the development of secondary sexual characteristics in males and females
- Adrenal androgen production regulated by ACTH (not pituitary gonadotrophins (LH/FSH)!!)
Manifestations of Congenital Adrenal Hyperplasia?
Disorders of sexual development due to adrenal androgen (DHEA) and/or estrogen secretion
Males
- precocious puberty in men (accelerated secondary sexual development)
- high incidence of infertility
Masculinisation (virilisation) in Women
- ambiguous genitalia
- excessive facial hair, virilization
- menstrual irregularity in adolescence
- anovulation in adulthood
Rapid early childhood growth but premature closure of epiphyseal growth plate and reduced adult stature
