Autonomous gonadotropin release from the human pituitary in vitro and factors influencing this secretion

Our understanding of the hypothalamus as the sole pacemaker for episodic hormone release has been challenged by recent observations of an autonomous rhythmic secretion from the pituitary, independent of hypothalamic inputs. Using an in vitro perifusion system, we were able to demonstrate an intrinsically pulsatile gonadotropin secretion from human fetal and adult pituitaries. This high-frequency/low-amplitude release is calcium-dependent and stimulated by gonadotropin releasing hormone (GnRH) administrations. Also, the autonomous release of luteinizing hormone (LH) appears to be temporally and functionally linked to the spontaneously pulsatile secretion of other anterior pituitary hormones, suggesting the existence of a common intrapituitary mechanism entraining these hormone pulsatilities. Further, the spontaneous and GnRH-stimulated LH release is greater from human female fetal pituitaries than from male fetal pituitaries at mid-gestation, presumably a reflection of differences in the negative feedback actions by factors from the fetal gonads. Collectively, we have observed an autonomous gonadotropin release from the human pituitary independent of, but facilitated by, GnRH. This spontaneous pulsatile secretion is calcium-dependent and entrained to the release of other anterior pituitary hormones. Therefore, it may represent the activity of a common intrapituitary pulse-generating mechanism and its modulation by factors from inside and outside the human pituitary.