Modulation of gonadotropin secretion by corticosterone: interaction with gonadal steroids and mechanism of action.

The effects of corticosterone (B) on pituitary responsiveness to LHRH and on gonadal steroid modulation of gonadotropin secretion were investigated using primary cultures of rat pituitary cells. Cultures were treated for 2 days with steroids and then challenged with LHRH for 4 h. B inhibited LH secretion, increasing the EC50 for LHRH from 1.40 to 4.96 nM. The reduction in LH release was accompanied by an increase in cell LH, so that the total amount of LH present in the cultures was unchanged. The EC50 for the effect of B on LH secretion was 0.57 microM. B increased the total amount of FSH present in the cultures. At high concentrations of B (10-100 microM), this effect was associated with an increase in FSH secretion. Testosterone inhibited LH secretion in both the absence and the presence of B. B had no effect in the presence of maximal concentrations of testosterone but augmented the inhibitory effect of lower concentrations. Estradiol (E) stimulated LH secretion in both the absence and the presence of B. However, the stimulatory effect of E was reduced by B, so that cultures treated with both B and E secreted no more LH than untreated cultures. B inhibited the LH secretory responses to Ca2+ influx and protein kinase C activation but did not affect the response to arachidonic acid, suggesting that the mechanism of B action may involve an inhibition of arachidonic acid release. Together these results indicate that the inhibitory effects of stress on reproduction are mediated at least partially by the inhibitory effects of B on LH secretion.