Gonadal Hormones Flashcards
Reminder: outline the effects of the pituitary hormones
ANTERIOR PITUITARY HORMONES =
GnRH —> LH & FSH —> Ovaries/Testes —> Oestrogens & Ovulation/Androgens & Spermatogenesis
GHRH —> GH —> Liver —> Insulin-like Growth Factor
(inhibited by somatostatin)
Prolactin (pituitary gland) —> breasts/gonads —> Lactation (+ sexual refractory period?)
(inhibited by dopamine - hypothalamus)
TRH —> TSH —> thyroid —> T3 & T4
(inhibited by somatostatin)
CRH —> ACTH —> adrenal glands —> corticosteroids
POSTERIOR PITUITARY HORMONES =
ADH —> increased water reuptake in late DCT & collecting duct
(also stimulates increased ACTH production)
Oxytocin —> breasts/uterus —> let-down reflex/uterine contraction (+ sexual arousal?)
Reminder: list the glycoproteins and polypeptide hormones produced by the pituitary gland.
Glycoprotein hormones =
- FSH & LH (gonadotrophs)
- TSH (thyrotrophs)
Polypeptide hormones =
- GH (somatotrophs)
- ACTH (corticotrophs)
- Prolactin (lactotrophs)
Outline the male hypothalamic-pituitary-gonadal axis.
FSH stimulates Sertoli cells (in spermatic tubules) to produce:
- oestradiol (converted from testosterone; directs spermatogenesis)
- androgen binding protein (necessary for testosterone to pass the spermatic barrier into the Sertoli cells)
- inhibin (inhibitory effect on ant. pituitary gland to reduce FSH secretion only - controls rate of spermatogenesis)
- anti-Müllerian inhibiting hormone (during embryogenesis)
LH stimulates Leydig cells (in blood vessels outside spermatic tubules) to produce:
- androgens (inhibitory effect on hypothalamus & ant. pituitary gland; reduces the AMOUNT of LH & FSH secreted but reduces the EFFECT of GnRH)
- –> pass into Sertoli cells for spermatogenesis (occurs continuously)
note: testosterone levels are constant in the long term, but vary in the short term due to circadian rhythm & environmental stimuli e.g. sexual images/thoughts
note: testosterone has determinative effects (irreversible development of secondary sexual characteristics) and regulatory effects (maintains adult reproductive system)
Outline the female hypothalmic-pituitary-gonadal axis.
FSH stimulates granulosa cells to produce:
- oestrogens
= moderate amount of oestrogen reduces amount of GnRH secreted per pulse, but above a critical threshold increases the amount of GnRH secreted —> LH surge —> ovulation
= same effect on LH & FSH secretion as long as progesterone is absent - activin (stimulates ant. pituitary gland)
- inhibin (inhibits FSH secretion by ant. pituitary gland)
LH stimulates theca cells (theca interna) to produce:
- androgens (converted to oestrogens by granulosa cells after ovulation)
- progestins (can stimulate or inhibit the hypothalamus, stimulates the ant. pituitary?)
= progesterone increases the inhibitory effects of moderate amounts of oestrogen
= progesterone prevents positive feedback of high amount of oestrogen, preventing ovulation
What are the effects of oestrogen in the follicular phase of the menstrual cycle?
- Fallopian tube: facilitates movement of ovum to body of uterus
- thickening of endometrium & secretion of fluid (nourishes & stimulates sperm)
- growth & motility of myometrium (contraction propels fluid to site of fertilisation)
- thin, alkaline cervical mucus produced (attracts sperm & allows movement into uterus)
- epithelial thickening in vagina
- changes in skin, hair, and metabolism (increases chances of intercourse)
- calcium metabolism changes
What is the effect of LH on the ovulatory follicles present in the different parts of the menstrual cycle?
Pre-ovulation: increased LH —–> weakens theca externa ——> follicle ruptures (ovulation)
Luteal phase: LH —> maintains corpus luteum —-> secretes progesterone and some oestrogen
What are the effects of progesterone on oestrogen-primed cells in the luteal phase of the menstrual cycle?
- further thickening of endometrium into secretory form (sustains conceptus, stimulates implantation & growth)
- thickening of myometrium & reduction in motility (conceptus is not expected)
- thick, acid cervical mucus (protects internal environment from bacterial infections & prevents multiple fertilisation)
- changes in mammary tissue, increased body temp., metabolic changes, electrolyte changes —> fluid retention (all in preparation for pregnancy)
Reminder: contrast the structure of the anterior and posterior lobes of the pituitary gland.
ANTERIOR =
- purely endocrine gland: neurosecretory cells of hypothalamus produce releasing hormones which stimulate secretion of pituitary hormones
- pituitary hormones secreted directly into hypophyseal portal system
- arises from Rathke’s pouch (depression in roof of developing mouth in front of buccopharyngeal membrane - ectoderm)
POSTERIOR =
- neurosecretory endocrine gland: neurosecretory cells of hypothalamus move into the pituitary gland itself to produce pituitary hormones
- axons of neurosecretory cells in contact with blood vessels in pituitary gland
- arises from extension of ventral brain (ectoderm)
What are the initial and longterm effects of menopause on the hypothalamic-pituitary-gonadal axis?
Menopause = dramatically less oestrogen secreted
Initially: loss of oestrogen negative feedback on hypothalamus and anterior pituitary gland —> increase in FSH, LH, & GnRH
Several years post-menopause —> hormones return to lower levels
note: LH only affected by loss of oestrogen negative feedback, FSH also affected by reduction in inhibin (selectively inhibits FSH) —> more FSH is secreted initially
What are the effects of pregnancy on the hypothalamic-pituitary-gonadal axis?
Placenta secretes human chorionic gonadotrophin
Placenta secretes oestrogen & progesterone
- progesterone inhibits hypothalamus and pituitary gland
- oestrogen inhibits hypothalamus and pituitary gland (independent of LH & FSH)
—> reduction in FSH, LH, & GnRH
Give an example of an anti-oestrogen. What effects does this have on the hypothalamic-pituitary-gonadal axis?
Clomiphene (infertility drug) inhibits replenishment of oestrogen receptors
Mimics effect of menopause: initial decrease and then increase in GnRH, FSH, & LH
What would be the effect of a constant dose of a progesterone-like drug?
Low dose: anti-contraceptive e.g. microgynon
No inhibition of LH surge —> ovulation will probably still occur
BUT progestrogens affect the cervical mucus to inhibit sperm transport (thicker & more acidic)
High dose: anti-contraceptives containing desogesterel
Reduced gonadotrophin secretion —> reduction in oestrogen —> enhances negative feedback of oestrogen —> reduction in LH & FSH secretion —> inhibits positive feedback of oestrogen —> no LH surge —> no ovulation, no follicular development (therefore contraceptive)
Give some examples of drugs which mimic and antagonise the effects of dopamine on prolactin.
Bromocriptine mimics dopamine —> inhibits prolactin secretion
Metoclopramide antagonises dopamine —> increases prolactin secretion —> increases GnRH release —> reduces fertility (causes anovulation and sometimes amenorrhoea)
Summarise the effects of the gonadal hormones and their target tissues.
FSH —> Sertoli cells —> nourishes spermatozoa & creates haemato-testicular barrier
—> granulosa cella —> convert androgens (from theca) to oestradiol
LH —> Leydig cells —> testosterone secretion
—> thecal cells —> androgen secretion
