Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, UK.
J Neuroendocrinol. 2009 May;21(5):457-64. doi: 10.1111/j.1365-2826.2009.01864.x.
Rapid but often transient changes in mitotic and apoptotic activity are important components of the pituitary response to changes in the hormonal environment. For example, bilateral adrenalectomy and orchidectomy each result in a wave of increased mitosis lasting approximately 1 week, mediated by the same population of trophically active and, to a large extent, endocrinologically inactive cells. By 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 aimed 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, which resolved within 7 days as expected, whereas oestrogen induced a significant increase in mitotic activity, which 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 compared 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 is 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-, adrenocorticotrophic hormone- and luteinising hormone-negative cells that respond mitotically to adrenalectomy. Oestrogen therefore has a previously unrecognised non-cell type-specific trophic effect in the pituitary that 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.
有丝分裂和细胞凋亡活性的快速但通常是短暂的变化是垂体对激素环境变化反应的重要组成部分。例如,双侧肾上腺切除术和睾丸切除术都会导致持续约 1 周的有丝分裂增加波,这是由同样的具有营养活性的、在很大程度上内分泌不活跃的细胞介导的。与这些垂体营养活性的紧张抑制剂相反,关于妊娠期间催乳素细胞数量逐渐增加的报告表明,雌激素是一种有效的、持久的垂体有丝分裂原。通过比较雄性大鼠垂体前叶有丝分裂对雌激素处理、肾上腺切除术和两者结合的反应幅度和持续时间,本研究旨在进一步阐明雌激素诱导的营养反应的特征,特别是催乳素细胞是否是主要涉及的细胞类型。肾上腺切除术产生了一波有丝分裂活性增加,如预期的那样,在 7 天内得到解决,而雌激素诱导了显著的有丝分裂活性增加,在研究的 14 天内持续存在。结合肾上腺切除术和雌激素处理的营养作用不是累加的,因为与单独雌激素处理相比,在最初几天有丝分裂指数的统计学上不显著的上升趋势完全被雌激素预处理所消除。无论是在有或没有肾上腺切除术的情况下,雌激素诱导的催乳素细胞有丝分裂活性的增加并没有导致研究结束时与催乳素阴性垂体实质细胞数量相比,催乳素阳性细胞数量的相对大小增加。尽管在妊娠期间报道了催乳素细胞数量的显著增加,但这些数据表明,至少在药物剂量的雌激素作用的早期(即在 2 周内),相对于其他细胞亚群,催乳素细胞亚群的有丝分裂反应仅增加 5-8%。出乎意料的是,雌激素的有丝分裂反应主要发生在不含有催乳素的细胞中,并导致除其他营养反应性群体外,对肾上腺切除术有丝分裂反应的整个催乳素、促肾上腺皮质激素和黄体生成素阴性细胞亚群的招募。因此,雌激素在垂体中具有以前未被认识到的非细胞类型特异性营养作用,通过诱导催乳素阴性细胞数量的同时增加,掩盖了催乳素细胞群体的相对扩张,其性质至少部分仍有待确定。