Steroid hormone dysregulation Flashcards
describe the follicular/proliferative stage of the menstrual cycle
maturation of ovarian follicles to prepare for ovulation
as the dominant follicle grows it secretes growing levels of oestradiol
this inhibits growth of other follicles;
thinning of the cervical mucus
causes endometrial stromal cell proliferation
peak oestradiol causes LH surge, resulting in ovulation
describe the luteal/secretory phase
formation of corpus luteum - increasing progesterone (and oestradiol) induces decidualisation and endometrial receptivity
if there is no fertilisation, corpus luteum regresses - withdrawal of progesterone causes spiral arteries to constrict and endometrial ischaemia, this causes cell deathand menses
what can disturbance of endometrial receptivity lead to
endometrial functional inadequacy (implantation failure, pregnancy loss, gynaecological disorders)
this can lead to further adverse consequences on events later in gestation (recurrent miscarriage, pre-eclampsia, intrauterine growth restriction)
what causes implantation failure
progesterone or oestrogen imbalance results in impaired induction of endometrial receptivity
can also shift the timing so there is not synchrony during the window of implantation
what can uterine incompetence lead to
implantation failure, early spontaneous abortion, pregnancy loss, recurrent miscarriage, pre-eclampsia, IUGR (intrauterine growth restriction), preterm birth
what can poor implantation lead to
pregnancy loss, recurrent miscarriage, pre-eclampsia, IUGR, preterm birth
what can shallow trophoblast invasion and incomplete uterine vascular remodelling lead to
pre-eclampsia, IUGR, preterm birth, recurrent miscarriage
what is endometriosis
growth of endometrial tissue outside the uterus (peritoneal cavity, ovaries, intestines)
what causes endometriosis
endometrial cells shed via retrograde efflux during menstruation (menstrual backwash)
alteration in sex hormone signalling can lead to pro-inflammatory mediators at lesion sites
this can inhibit apoptosis, promote adhesion and proliferation of endometrial cells
can also promote angiogenic events and neurogenesis within the lesion
what is endometriosis characterised by
oestrogen-receptor beta overexpression(leads to sustained proinflammatory factor release) and reduced progesterone-receptor expression (E2 promotes inflammation, P4 has anti-inflammatory factor capacity, leads to E2 dependent and P4 resistant lesions)
what is cell proliferation driven by
endogenous and exogenous hormones
presents the opportunity for accumulation of random genetic errors
what do the majority of human breast cancers begin as
oestrogen dependent - oestrogens promote proliferation of breast epithelium
what is implicated in breast cancer progression
oestrogen signalling and oestrogen receptors
oestrogen-induced rapid ER-alpha signalling facilitates cell migratory functions and cell metastasis
PR-beta signalling can also contribute to breast cancer cell proliferation in response to progesterone
what is the function of ovarian hormones
regulate endometrial cell proliferation, regeneration and fucntion
what affects endometrial proliferation and cell survival
oestrogen (and insulin) in excess and lack of progesterone
results in increasing the risk of epithelial transformation/carcinogenesis
