Estradiol up-regulation of pituitary progesterone binding is required for progesterone inhibition of luteinizing hormone release.

This study examines the regulation of progesterone receptor (PR) in the inhibition of pituitary luteinizing hormone (LH) secretion. Ovariectomized ewes underwent hypothalamic-pituitary disconnection, were pulsed with gonadotropin-releasing hormone (GnRH) and received 1 of 4 treatments: estradiol alone (E), estradiol priming before progesterone (E+P), E removed and replaced with P (E-P), or no steroids (C). P treatment for 24 h, with E or following E-priming, reduced LH pulse amplitude by 55% (p<0.05). E alone did not affect LH release. E increased pituitary cytosolic P binding capacity fourfold over controls (p<0.01) and P further increased binding to eight times controls (p<0.01). Pituitary PR mRNA increased to 149 and 171% of C in E and E+P groups, respectively (p<0.05), but E removal resulted in PR mRNA levels not different from controls. Pituitary receptors for GnRH were tripled by E alone compared to C (p<0.01), whereas P alone or with E had no effect. These data suggest an E-induced, direct pituitary inhibition of LH secretion by P and that this effect of P is associated with E-enhanced binding of P in the pituitary. Additionally, the direct pituitary effects of P on LH secretion cannot be accounted for by influences on GnRH receptor numbers.