The trophic effects of oestrogen on male rat anterior pituitary lactotrophs

Rapid but often transient changes in mitotic and apoptotic activity are important components of the pituitary response to changes in the hormonal environment. Bilateral adrenalectomy and orchidectomy, for example, each result in a wave of increased mitosis lasting approximately a week, mediated by the same population of trophically active and to a large extent endocrinologically inactive cells. In contrast to these tonic inhibitors of pituitary trophic activity, reports of a progressive increase in lactotroph numbers during pregnancy suggest that oestrogen is a potent and persistent pituitary mitogen. By comparing the amplitude and duration of male rat anterior pituitary mitotic responses to oestrogen treatment, to adrenalectomy and to a combination of the two, the present study was designed to further clarify the characteristics of the oestrogen-induced trophic response, in particular whether lactotrophs are the predominant cell type involved. Adrenalectomy produced a wave of increased mitotic activity that resolved within 7 days as expected, whereas oestrogen induced a significant increase in mitotic activity that was sustained for the 14 day duration of the study. The trophic effects of combining adrenalectomy and oestrogen treatment were not additive in that the statistically insignificant upward trend in mitotic index during the first few days in comparison to oestrogen treatment alone was entirely abolished by oestrogen pre-treatment. The increase in mitotic activity in lactotrophs induced by oestrogen either with or without adrenalectomy did not result in an increase in the relative size of the prolactin positive compared to prolactin negative pituitary parenchymal cell numbers by the end of the study. Despite the marked increase in the lactotroph population that has been reported during pregnancy, these data indicate that at least the early (i.e. within 2 weeks) mitotic response to pharmacological doses of oestrogen increases mitotic activity in the lactotroph subpopulation by only 5-8% relative to other cellular subpopulations. Unexpectedly, the mitotic response to oestrogen principally occurs in non prolactin-containing cells and results in the recruitment, amongst other trophically responsive populations, of the entire subpopulation of prolactin-, ACTH- and LH-negative cells that respond mitotically to adrenalectomy. Oestrogen therefore has a hitherto unrecognized non cell type-specific trophic effect in the pituitary which obscures the relative expansion of the lactotroph population by inducing concurrent increases in numbers of prolactin-negative cells, the nature of which at least in part remains to be determined.