Ovarian feedback, mechanism of action and possible clinical implications

Abstract

The secretion of gonadotrophins from the pituitary in women is under ovarian control via negative and positive feedback mechanisms. Steroidal and non-steroidal substances mediate the ovarian effects on the hypothalamic-pituitary system. During the follicular phase of the cycle, estradiol (E(2)) plays a key role, while circulating progesterone (at low concentrations) and inhibin B contribute to the control of LH and FSH secretion respectively. During the luteal phase, both E(2) and progesterone regulate secretion of the two gonadotrophins, while inhibin A plays a role in FSH secretion. The intercycle rise of FSH is related to changes in the levels of the steroidal and non-steroidal substances during the luteal-follicular transition. In terms of the positive feedback mechanism, E(2) is the main component sensitizing the pituitary to GnRH. Activity of a non-steroidal ovarian substance, named gonadotrophin surge-attenuating factor (GnSAF), has been detected after ovarian stimulation. It is hypothesized that GnSAF, by antagonizing the sensitizing effect of E(2) on the pituitary, regulates the amplitude of the endogenous LH surge at midcycle. Disturbances in the feedback mechanisms can occur in various abnormal conditions or after treatment with pharmaceutical compounds that interfere with the production or the action of endogenous hormones.

Estrogen receptor (ESR) 2 partially offsets the absence of ESR1 in gonadotropes of pituitary-specific Esr1 knockout female mice

“…Moreover, the absence of effects of OVX on gonadotrope size, and of ESR2 activation on Pgr expression at the time of the study, points to a mild E control of gonadotrope biology in the mouse. These findings confirm earlier data indicating differences in the gonadotrope biology between rats and mice (Abbot et al 1986, Turgeon et al 1999, 2006 and suggest that these two rodent species have adopted different reproductive strategies, which are further evidenced in the different response to pheromonal stimuli (Sánchez-Criado et al 1989). …”

“…Again, the situation is dissimilar to that of the OVX rat because ESR2 activation does induce Pgr expression (Sánchez-Criado et al 2004, 2006. In OVX WT mice, activation of ESR1 by E 2 induced Pgr expression in 38.4G2.6% of pituitary cells, while the average proportion of pituitary PGRpositive cells in the rat is about 10% (Sánchez-Criado et al 2005, 2006, Garrido-Gracia et al 2008). This difference is most likely due to the fact that in mice both gonadotropes and lactotropes express PGR .…”

“…Since GNRH1-secreting neurons do not express Esr1 (Shivers et al 1983), the question of the supra-pituitary level at which E 2 and PPT activate ESR1 arises. It seems reasonable to assume that ESR-mediated critical negative feedback is not exerted on GNRH1 neurons directly but rather transynaptically 554 J E Sánchez-Criado, K Trudgen and others through modulation of interneuron afferents from several hypothalamic E-sensitive presynaptic neurons expressing Esr1 both in rats (Levine 2000, Messinis 2006, Wintermantel et al 2006) and in mice (Yaghmaie et al 2010).…”

“…This action is evident in the decreasing effect of exogenous E on serum LH levels in ovariectomized (OVX) animals. However, the relative contribution of the pituitary to the inhibitory feedback by gonadotrope ESR remains unclear (Fink 1988, Messinis 2006.…”

Effect of water decoction of Langsat bark (Lansium domesticum Corr.) on estrous cycle and uterus weight in mice (Mus musculus L.)

“…12 Estrous cycle is a process that is controlled by various hormones, either hormones of the hypothalamus-pituitary and ovarian. These hormones 13 Ones of the chemical constituents of Langsat's Bark is Lansiolides triterpenoids. 2 The triterpenoid compounds have effects similar to estrogen.…”