OVARIAN-STEROIDS MODULATE ENDOTHELIN-INDUCED LUTEINIZING-HORMONE SECRETION FROM CULTURED RAT PITUITARY-CELLS

It has been demonstrated that endothelins (ETs) induce LH secretory re sponses in cultured rat pituitary cells. Because estradiol and progest erone are known to be potent modulators of GnRH-induced gonadotropin s ecretion, we examined whether these steroids also influence the secret ory responses of gonadotrophs to ETs. Cultured female rat pituitary ce lls were treated for 48 h with vehicle (0.2% ethanol), 1 nm estradiol alone, or a combination of 1 nm estradiol and 100 nm progesterone or f or 48 h with 1 nm estradiol and a further 4 h with 100 nm progesterone and subsequently stimulated with 10 pm-100 nm ET-1 or ET-3. Forty-eig ht-hour estradiol treatment led to enhanced LH secretory responses to both ETs. This action was facilitated by short term progesterone treat ment (3-fold vs. vehicle), while long term progesterone treatment was inhibitory. Perifusion experiments were performed to study the kinetic s of individual and pulsatile LH secretory responses after steroid exp osure of pituitary cells. ET-1 induced immediate biphasic LH responses that were augmented by long term estradiol treatment. Two-hour proges terone exposure led to marked increases in LH secretion, whereas 48-h progesterone treatment was inhibitory. Estradiol and progesterone were able to modulate both the initial spike and the secondary plateau pha se of the secretory profile in response to ET-1, although these action s did not always reach statistical significance. The steroid treatment paradigms employed also induced inhibitory and stimulatory effects in cells that were stimulated with ET-3 in a pulsatile fashion. In these experiments it could be demonstrated that the facilitatory action of progesterone was present after 50 min of treatment and was maximum aft er 150 min (5-fold enhancement). The present data support the hypothes is that ETs are involved in the physiological regulation of gonadotrop in secretion and demonstrate that ovarian steroids can act as potent m odulators of ET-induced LH secretion.