Gonadotropin-releasing hormone-induced stimulation and desensitization of free α- subunit secretion mirrors luteinizing hormone and follicle-stimulating hormone in perifused rat pituitary cells

A pulsatile pattern of hypothalamic GnRH stim-ulation is necessary for the maintenance of pituitary LH and FSH secretion, with continuous GnRH leading to a decrement in response. Although the physiological pattern of free α-subunit secretion closely mimics that of LH, several reports have indicated that free α-subunit is not desensitized by continuous GnRH stimulation. To explore the basis of this phenomenon, we have evaluated the responses of all three gonadotrope secretory products to carefully coordinated administrations of pulsatile and continuous GnRH in a dispersed rat pituitary perifusion system. Sensitivities (ED₅₀) to GnRH fell within a narrow range for free α-subunit (11.5 nM), LH (12.9 nM), and FSH (17.3 nM), although a greater mass of LH than free α-subunit or FSH was released after each pulse of GnRH. The response to a standard GnRH pulse (10 nM) administered every 15, 30, or 120 min for 9 h was very stable, with no evidence of priming, summation, or loss of response. LH, FSH, and free α-subunit did, however, show significantly (P < 0.05) higher pulse amplitudes with longer interpulse intervals. In contrast to previous observations in vivo, the three gonadotrope secretory products showed parallel desensitization in response to continuous infusions of GnRH. This loss of response was significant (P < 0.05) after exposure to as little as 0.1 (FSH) to 0.5 nM (LH and α-subunit) GnRH for 2 h or to higher concentrations of GnRH (10 nM) for as little as 15 min (LH, FSH, and a-subunit). These concentrations and durations of GnRH stimulation are within the range of values measured in vivo. We conclude that 1) free a-subunit, LH, and FSH have similar concentration and frequency responses to pulsatile GnRH, although the absolute amount of hormone released is different for each secretory product; 2) the frequency of pulsatile GnRH stimulation can function as an independent determinant of secretion for each of the three products; and 3) in contrast to observations in vivo, free a-subunit, LH, and FSH secretion desensitize similarly after exposure to concentrations or durations of GnRH that may occur in vivo. These observations raise the possibility that desensitization plays a role in the physiological regulation of gonadotrope secretion.