Local regulation of gonadotroph function by pituitary gonadotropin-releasing hormone

Cultured rat pituitary cells and immortalized pituitary gonadotrophs (alpha T3-1 cells) express specific messenger RNA transcripts for GnRH and exhibi t positive immunostaining for the GnRH peptide. Each cell type released GnR H during both static culture and perifusion, albeit in lesser amounts than cultured hypothalamic cells and GT1-7 neurons. In perifused pituitary cells , exposure to a GnRH agonist stimulated the release of GnRH as well as LH. In contrast, treatment with a GnRH receptor antagonist or with GnRH antiser um decreased basal LH release. In pituitary cell cultures, a small proporti on of gonadotrophs exhibited high amplitude and low frequency baseline Ca2 oscillations in the absence of GnRH stimulation. Such spontaneous oscillat ions were comparable to those induced by pico-molar concentrations of GnRH and could be abolished by treatment with a GnRH antagonist. These in vitro findings indicate that locally produced GnRH causes low level activation of pituitary GnRH receptors, induces spontaneous intracellular Ca2+ oscillati ons, and contributes to basal LH secretion in cultured pituitary cells. In vivo, such autocrine or paracrine actions of pituitary-derived GnRH could p rovide a mechanism for the maintenance of optimal responsiveness of the gon adotrophs to pulses of GnRH arising in the hypothalamus. The presence and a ctions of GnRH in the anterior pituitary gland, the major site of expressio n of GnRH receptors, suggest that local regulatory effects of the neuropept ide could supplement the primary hypothalamic mechanism for the control of episodic gonadotropin secretion.