Local Regulation of Gonadotroph Function by Pituitary Gonadotropin-Releasing Hormone

Cultured rat pituitary cells and immortalized pituitary gonado- trophs (aT3-1 cells) express specific messenger RNA transcripts for GnRH and exhibit positive immunostaining for the GnRH peptide. Each cell type released GnRH during both static culture and perifu- sion, 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 antiserum decreased basal LH release. In pituitary cell cultures, a small pro- portion of gonadotrophs exhibited high amplitude and low frequency baseline Ca21 oscillations in the absence of GnRH stimulation. Such spontaneous oscillations 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 re- ceptors, induces spontaneous intracellular Ca21 oscillations, and con- tributes to basal LH secretion in cultured pituitary cells. In vivo, such autocrine or paracrine actions of pituitary-derived GnRH could pro- vide a mechanism for the maintenance of optimal responsiveness of the gonadotrophs to pulses of GnRH arising in the hypothalamus. The presence and actions of GnRH in the anterior pituitary gland, the major site of expression of GnRH receptors, suggest that local regu- latory effects of the neuropeptide could supplement the primary hy- pothalamic mechanism for the control of episodic gonadotropin se- cretion. (Endocrinology 141: 1187-1195, 2000)