Kaiser U B, Jakubowiak A, Steinberger A, Chin W W
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Endocrinology. 1993 Aug;133(2):931-4. doi: 10.1210/endo.133.2.8393779.
The recent isolation of cDNAs encoding the rat pituitary gonadotropin-releasing hormone receptor (GnRHR) allows studies of the regulation of the synthesis of the GnRHR and its relationship to reproductive function. Analyses of the regulation of GnRHR mRNA levels in the rat pituitary in vivo revealed a progressive increase in levels to 2.0 +/- 0.2-fold after ovariectomy (OVX) and 5.2 +/- 1.3-fold after castration (CAST) (21 days post-operative), compared to intact adult female and male controls, respectively. Replacement therapy with 17 beta-estradiol benzoate in 21-day post-OVX female rats resulted in a marked decrease in GnRHR mRNA levels by 7 days, compared to controls. In contrast, therapy with testosterone propionate in 21-day post-CAST male rats resulted in only a modest decrease in GnRHR mRNA levels. Thus, manipulation of the reproductive endocrine system in vivo results in alterations in GnRHR synthesis at the pretranslational level, which parallel known changes in cell surface gonadotropin-releasing hormone (GnRH) binding activities. The treatment of superfused primary monolayer cultures of rat pituitary cells with hourly pulses of GnRH (10 nM, 6 min/h) resulted in a marked increase in GnRHR mRNA levels (12.8 +/- 4.3-fold compared to untreated cells). In contrast, treatment of cultured cells with continuous GnRH caused no change in GnRHR mRNA levels. These in vitro data show homologous regulation of GnRHR gene expression by GnRH, and suggest that the changes in GnRHR gene expression observed in vivo may be attributable at least in part to changes in the pattern of hypothalamic GnRH secretion.
最近分离出编码大鼠垂体促性腺激素释放激素受体（GnRHR）的cDNA，这使得对GnRHR合成的调节及其与生殖功能的关系的研究成为可能。对成年雌性和雄性大鼠垂体中GnRHR mRNA水平的体内调节分析显示，与完整的成年雌性和雄性对照相比，卵巢切除（OVX）后GnRHR mRNA水平逐渐升高至2.0±0.2倍，阉割（CAST）后（术后21天）升高至5.2±1.3倍。在21天卵巢切除后的雌性大鼠中用苯甲酸雌二醇进行替代治疗，与对照相比，7天后GnRHR mRNA水平显著降低。相反，在21天阉割后的雄性大鼠中用丙酸睾酮治疗，GnRHR mRNA水平仅适度降低。因此，体内生殖内分泌系统的调控导致翻译前水平的GnRHR合成发生改变，这与已知的细胞表面促性腺激素释放激素（GnRH）结合活性的变化平行。用每小时脉冲式给予GnRH（10 nM，6分钟/小时）处理大鼠垂体细胞的超融合原代单层培养物，导致GnRHR mRNA水平显著升高（与未处理细胞相比为12.8±4.3倍）。相反，用持续的GnRH处理培养细胞，GnRHR mRNA水平没有变化。这些体外数据显示GnRH对GnRHR基因表达的同源调节，并表明在体内观察到的GnRHR基因表达变化可能至少部分归因于下丘脑GnRH分泌模式的变化。
