Heterogeneity of pituitary lactotrophs: immunocytochemical identification of functional subtypes.

The existence of functional lactotroph subpopulations was confirmed in primary pituitary cell cultures of female rats submitted to estrogen treatment and stimulation with thyrotrophin releasing hormone (TRH) and angiotensin II (A-II). In cell cultures of pituitary tissue, prolactin (PRL) producing cells represent about 50% of the total cell count, most of which (90%) correspond to a typical lactotroph subpopulation characterized by large secretory granules, 500-900 nm in diameter, and well developed rough endoplasmic reticulum (RER) and Golgi complex. Few atypical lactotrophs were detected with a quiescent appearance and containing smaller secretory granules, often indistinguishable from granular content of other pituitary cells. Depletion of endogenous estrogen caused by ovariectomy (OVX) decreased the pituitary lactotroph population about 34%, with a relative increase of atypical forms (56%). Replacement therapy with benzoate estradiol (EB) to OVX rats did not reverse the proportion of typical and atypical lactotrophs gauged in control pituitary glands. The predominant lactotroph population of OVX rat was an atypical PRL producing cell which displayed a quiescent appearance compatible with a reduced secretory activity. By contrast, estrogen administration to OVX rats caused a striking development of the RER, a hypertrophy of the Golgi complex and an increased storage of mature and immature secretory granules in the majority of lactotrophs. These features are compatible with a reactivated protein synthesis. Estrogen also enhanced significantly (p < 0.05) the responsiveness of lactotrophs to A-II and the PRL secretion in both intact and OVX + EB treated rats increased by 40% and 30% respectively. By contrast, A-II did not produce any statistically significant response of lactotrophs from OVX female rats. At variance to this observation, in all models tested TRH increased significantly the PRL secretion (p < 0.05). The correlation of PRL secretion and morphology of different lactotroph subtypes authenticates the existence of a lactotroph subpopulation unresponsive to A-II in pituitary cell cultures from rats depleted of estrogen.