Department of Endocrinology, Institute of Functional Genomics, 34094 Montpellier, France.
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21878-83. doi: 10.1073/pnas.1010849107. Epub 2010 Nov 22.
There are well-recognized sex differences in many pituitary endocrine axes, usually thought to be generated by gonadal steroid imprinting of the neuroendocrine hypothalamus. However, the recognition that growth hormone (GH) cells are arranged in functionally organized networks raises the possibility that the responses of the network are different in males and females. We studied this by directly monitoring the calcium responses to an identical GH-releasing hormone (GHRH) stimulus in populations of individual GH cells in slices taken from male and female murine GH-eGFP pituitary glands. We found that the GH cell network responses are sexually dimorphic, with a higher proportion of responding cells in males than in females, correlated with greater GH release from male slices. Repetitive waves of calcium spiking activity were triggered by GHRH in some males, but were never observed in females. This was not due to a permanent difference in the network architecture between male and female mice; rather, the sex difference in the proportions of GH cells responding to GHRH were switched by postpubertal gonadectomy and reversed with hormone replacements, suggesting that the network responses are dynamically regulated in adulthood by gonadal steroids. Thus, the pituitary gland contributes to the sexually dimorphic patterns of GH secretion that play an important role in differences in growth and metabolism between the sexes.
在许多垂体内分泌轴中，存在着公认的性别差异，这些差异通常被认为是由性腺类固醇对神经内分泌下丘脑的印记产生的。然而，生长激素 (GH) 细胞排列在功能组织的网络中这一认识，提出了这样一种可能性，即网络的反应在男性和女性之间是不同的。我们通过直接监测从雄性和雌性小鼠 GH-eGFP 垂体切片中获得的单个 GH 细胞群体对相同的生长激素释放激素 (GHRH) 刺激的钙反应来研究这一点。我们发现，GH 细胞网络的反应存在性别二态性，雄性中反应细胞的比例高于雌性，与雄性切片中 GH 释放的增加相关。在一些雄性中，GHRH 会引发钙峰活动的重复波，但在雌性中从未观察到。这不是由于雄性和雌性小鼠之间的网络结构存在永久性差异；相反，对 GHRH 有反应的 GH 细胞比例的性别差异通过青春期后性腺切除术发生改变，并通过激素替代逆转，这表明网络反应在成年期受到性腺类固醇的动态调节。因此，垂体有助于 GH 分泌的性别二态模式，这在性别之间的生长和代谢差异中起着重要作用。
