Simonian S X, Murray H E, Gillies G E, Herbison A E
Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge, United Kingdom.
Endocrinology. 1998 Mar;139(3):1420-8. doi: 10.1210/endo.139.3.5814.
The sexually dimorphic profile of GH secretion is thought to be engendered by gonadal steroids acting in part on hypothalamic periventricular somatostatin (SOM) neurons. The present study set out to examine and characterize the development of sex differences in these SOM neurons. In the first series of experiments, we used in situ hybridization to examine SOM messenger RNA (mRNA) expression within the periventricular nucleus (PeN) of male and female rats on postnatal day 1 (P1), P5, and P10. Cellular SOM mRNA content was found to increase from P1 to P10 in both sexes (P < 0.01), but was 24% (P < 0.05) and 38% (P < 0.01) higher in males on P5 and P10, respectively. A second series of experiments examined the SOM peptide content of the PeN in developing rats and found increasing levels from P1 to P10, with a 44% higher SOM content in males compared with females on P10 (P < 0.05). The third series of experiments questioned the role of gonadal steroids in engendering sex differences in SOM mRNA expression by determining the effects of neonatal gonadectomy (GDX) and replacement of dihydrotestosterone or estradiol benzoate. The SOM mRNA content of PeN neurons in P5 males gonadectomized on the day of birth was the same as that in P5 females and was significantly reduced compared with that in sham-operated P5 males (P < 0.05). Male rats GDX on P1 and treated with estradiol benzoate from P1 to P5 had cellular SOM mRNA levels similar to those in intact males on P5, whereas dihydrotestosterone treatment had no effect. Treatment of intact males with an androgen receptor antagonist, cyproterone acetate, on P1 had no effect on cellular SOM mRNA on P5, whereas male rats given the aromatase inhibitor 1,4,6-androstatriene-3,17-dione from P1 to P5 had lower (P < 0.05) SOM mRNA levels than controls. In the final set of experiments, dual labeling immunocytochemistry showed that SOM neurons in the PeN of P5 rats did not contain estrogen receptor-alpha, but expressed androgen receptors in a sexually dimorphic manner. These results demonstrate that a sex difference in SOM biosynthesis, which persists into adulthood, develops between P1 and P5 in PeN neurons. Despite the absence of estrogen receptor-alpha in these neurons, the organizational influence of testosterone only occurs after its aromatization to estrogen.
生长激素（GH）分泌的性别差异特征被认为部分是由性腺类固醇作用于下丘脑室周生长抑素（SOM）神经元所导致的。本研究旨在检测并描述这些SOM神经元中性别差异的发展情况。在第一组实验中，我们采用原位杂交技术检测出生后第1天（P1）、P5和P10的雄性和雌性大鼠室周核（PeN）内SOM信使核糖核酸（mRNA）的表达。结果发现，两性的细胞SOM mRNA含量均从P1到P10增加（P < 0.01），但在P5和P10时，雄性分别比雌性高24%（P < 0.05）和38%（P < 0.01）。第二组实验检测了发育中大鼠PeN的SOM肽含量，发现从P1到P10含量增加，在P10时，雄性的SOM含量比雌性高44%（P < 0.05）。第三组实验通过确定新生期去势（GDX）以及二氢睾酮或苯甲酸雌二醇替代的影响，探讨了性腺类固醇在导致SOM mRNA表达性别差异中的作用。出生当天接受去势的P5雄性大鼠PeN神经元的SOM mRNA含量与P5雌性大鼠相同，与假手术的P5雄性大鼠相比显著降低（P < 0.05）。P1接受去势并从P1到P5用苯甲酸雌二醇处理的雄性大鼠，其细胞SOM mRNA水平与P5完整雄性大鼠相似，而二氢睾酮处理则无影响。P1用雄激素受体拮抗剂醋酸环丙孕酮处理完整雄性大鼠，对P5时的细胞SOM mRNA无影响，而从P1到P5给予芳香化酶抑制剂1,4,6-雄甾三烯-3,17-二酮的雄性大鼠，其SOM mRNA水平比对照组低（P < 0.05）。在最后一组实验中，双重标记免疫细胞化学显示，P?5大鼠PeN中的SOM神经元不含有雌激素受体α，但以性别差异的方式表达雄激素受体。这些结果表明，PeN神经元中SOM生物合成的性别差异在P1到P5之间形成，并持续到成年期。尽管这些神经元中不存在雌激素受体α，但睾酮的组织学影响仅在其芳香化为雌激素后才会出现。
