Wu J C, Sealfon S C, Miller W L
Department of Biochemistry, North Carolina State University, Raleigh 27695-7622.
Endocrinology. 1994 Apr;134(4):1846-50. doi: 10.1210/endo.134.4.8137751.
GnRH regulates the synthesis and secretion of pituitary gonadotropins. The number of receptors for GnRH (GnRH-rec) can vary from 500 to 15,000-20,000/gonadotrope in ovine pituitary cultures after treatment with physiologically relevant combinations of gonadal hormones. This large range suggests that regulation of GnRH-rec expression may be an important control point in GnRH action at the pituitary level. Reported here are the changes in GnRH-rec mRNA associated with pituitary treatments (48 h) of 17 beta-estradiol (E), progesterone (P), and an enriched preparation of porcine follicular inhibin (IN). Northern blot analysis was used to detect 3 species of GnRH-rec mRNA in primary ovine pituitary culture [5.5 kilobases (kb; 32%), 3.6 kb (51%), and 1.4 kb (17%)]; all were changed in parallel by E, P, and IN. GnRH-rec mRNAs were increased 190% over control levels after treatment with either E or IN, and 400% with E and IN combined; when E and IN were added along with P, the increase was only 50% (P caused an 87% inhibition of E plus IN induction). The addition of P in the absence of any other treatment reduced levels of GnRH-rec mRNA by 50%. Studies were also conducted with GnRH agonists (GnRH-A) due to their widespread clinical use for down-regulating reproductive function in men and women. The addition of GnRH-A to cultures was as effective as P in blocking E plus IN induction of GnRH-rec mRNA. In vivo studies in wethers showed that 7 days of chronic treatment with GnRH-A decreased all sizes of ovine GnRH-rec mRNA by 84-89%. These data indicate that E, P, and IN change GnRH-rec levels at least in part by changing levels of GnRH-rec mRNAs. They also show that GnRH-A can almost entirely block E plus IN induction of GnRH-rec mRNA in vitro and decrease levels of GnRH-rec mRNA in vivo in wethers.
促性腺激素释放激素（GnRH）调节垂体促性腺激素的合成与分泌。在用性腺激素的生理相关组合处理后，绵羊垂体培养物中促性腺激素释放激素受体（GnRH-rec）的数量在每促性腺细胞500至15,000 - 20,000个之间变化。如此大的范围表明，GnRH-rec表达的调节可能是GnRH在垂体水平发挥作用的一个重要控制点。本文报道了与垂体用17β-雌二醇（E）、孕酮（P）和猪卵泡抑制素浓缩制剂（IN）处理（48小时）相关的GnRH-rec mRNA的变化。采用Northern印迹分析检测原代绵羊垂体培养物中的3种GnRH-rec mRNA [5.5千碱基（kb；32%）、3.6 kb（51%）和1.4 kb（17%）]；E、P和IN对它们的影响是平行的。用E或IN处理后，GnRH-rec mRNA比对照水平增加了190%，E和IN联合处理时增加了400%；当E和IN与P一起添加时，增加仅为50%（P对E加IN诱导有87%的抑制作用）。在无任何其他处理的情况下添加P可使GnRH-rec mRNA水平降低50%。由于促性腺激素释放激素激动剂（GnRH-A）在临床上广泛用于下调男性和女性的生殖功能，因此也进行了相关研究。向培养物中添加GnRH-A与P在阻断E加IN诱导GnRH-rec mRNA方面效果相同。对去势公羊的体内研究表明，用GnRH-A慢性处理7天可使所有大小的绵羊GnRH-rec mRNA减少84 - 89%。这些数据表明，E、P和IN至少部分通过改变GnRH-rec mRNA水平来改变GnRH-rec水平。它们还表明，GnRH-A在体外几乎可以完全阻断E加IN诱导GnRH-rec mRNA，并在体内降低去势公羊GnRH-rec mRNA的水平。
