sex hormones Flashcards
what is function of GnRH, where is it secreted
gonadotropin releasing hormone (GnRH)
secreted by hypothalamus
controls secretion of FSH and LH
pulsating levels of GnRH stimulates FSH/LH production
continuous levels of GnRH inhibits FSH/LH production
how are GnRH agonists/antagonists used clinically
agonists are used with pulsating doses to treat infertility
used with continuous doses to inhibit FSH/LH release in treatment of androgen dependent prostsate cancer (to reduce circulating androgen levels)
continuous dosing is also used to control ovulation in assisted reproductive technology
GnRH antagonists also used to inhibit FSH/LH release for reasons above
what are gonadotropins, where are they secreted and what is their function
they are glycoproteins, all have common alpha subunit, differ in their beta subunit
FSH and LH secreted by anterior pituitary
chorionic gonadotropin is released by placenta
in females gonadotropins are involved in cyclic control of ovarian follicle development as well as oestrogen and progesterone secretion
in males FSH controls spermatogenesis and LH controls secretion of testosterone
what are uses of gondatropins therapeutically
LH and FSH used formale infertility due to pituitary insufficiency
they are used with GnRH agonists/antagonists for controlled ovulation
pregnancy tests dected cCG in urine
what are oestrogen, give examples where are they secreted
oestradiol, oestron and oestriol
steroids synthesised from androgens, mainly in the ovary
2 oestrogen receptors: ERalpha and ERbeta, both are intracellular nuclear receptors
third receptor is GPER1 and is a GPCR
what are actions of oestrogens
developement of female reproductive organs and secondary sex characteristics
in menstrual cycle has feedback control of gonadotropin secretion, negative feedback at low oestrogen concentrations and positive feedback at high concentrations
also promotes endometrial proliferation and increased expression of progesterone receptors
stimulate cervical mucuous glands to produce high volume, low viscosity, sperm friendly secretion
maintain vascular function: reduce capillary fragility, preserve vasodilator functions
causes salt and water retention, anabolic metabolic effects
reduces bone resorption
CV effects: increased blood coagulation, increased HDL and lowers LDL and cholesterol
how are oestrogens used therapeutically
ethinyloestradiol is pharmacological preparation, is orally active
contraception use in combination with progesterone
used by itself in hormone replacement therapy, can be used in combination with progesterone
what are oestrogen modulators
clomiphene: oestrogen antagonist, acts on receptors in pituitary and hypothalamus, provents negatiive feedback on GnRH and gonadotropin release, used to induce ovulation in some cases of infertility
tamoxifen: selective oestrogen receptor modulator (SERM), acts differently at different tissues (antagonists in breast, partial agonist at bones, liver and uterus)
used to treat oestrogen dependent breast cancer, however has been linked to increased risk of endometrial cancer and thromboembolic disease
raloxifine:
selective oestrogen receptor modulator (SERM)
antagonist in breast and uterus, partial agonist in bones and liver
used to prevent oestrogen receptor positive breast cancer in women at high risk, also used for treating postmenopausal osteoporosis
what are progestogens, where are they secreted
natural hormone is steroid hormone progesterone secreted by ovary and corpus luteum following LH receptor activation
large amounts of progesterone secreted by placenta during pregnancy
receptors are intracellular nuclear receptors
what are physiological actions of progestogens
control of menstrual cycle: promotes secretory phase of endometrial development in second half of cycle (vascularisatoin and development of nutrient rich secretion which favour implantation)
following lack of progesterone results in menstruation
modulates activity of cervical mucuous glands, reduces volume and increases viscocity of secretion
negative feedback effects on GnRH, reduces frequency of pulses, causes negative feedback on FSH and LH release due to amplitude of pulses
in pregnancy acts on uterus and mammary tissue
what are pharmacological preparations of progestogens
norethisterone: given orally or as depot injection, used in contraception and hormone replacement therapy
mefiprestone: progesterone antagonist, acts on receptors in uterus, causing endometrial breakdown and prostaglandin sensitisation, also used in early abortion along with prostaglandin
what is combined oral contraceptive pill, how does it work
contains oestrogen and progesterone, pill is take for 21 days and then 7 pill free/placebo days
example of oestrogens used in combined pill are: ethinyloestradiol
example progestogens used in combined pill are : norethisterone
mode of action: in follicular phase low oestrogen and progestogen suppress release of FSH and LH and therefore inhibit early development of follicle
there is no follicular oestrogen production so no mid cycle LH surge which means ovulation does not occur (mid cycle LH surge stimulates ovulation)
progestogen inhibits mid cycle LH production by decreasing GnRH pulse frequency
progestogen also makes mucus less suitable for passage of sperm
oestrogen and progestogen present together prevent normal endometrial development so conditions are not favourable for implantation
what are adverse effects of combined oral contraceptive pill
risk of thromboembolic disease in low reproductive age women, but increased by combined pill use
hypertension
increased risk of cervical cancer, although ovarian and endometrial cancer is reduced
what is progestogen only pill
continuous administration of progestogen only
mode of action is mainly on uterus:
reduction in volume and increased viscosity of secretions make conditions unfavourable for fertilisation
continuous progestogen prevents physiological endometrial development and so prevents implantation
some formulations reliably inhibit ovulation via negative feedback at hypothalamus and anterior pituitary
doses are only marginally above threshold required for adequate contraception and half life is brief, so missing a dose can result in conception
does not interfere w lactation
what are adverse effects of progestogen only pill
decreased bone density possibly related to reduced endogenous oestrogen levels causing oesteoporosis
