Kovács M, Koppán M, Mezó I, Teplán I
Department of Anatomy, University Medical School, Pécs, Hungary.
Acta Biol Hung. 1994;45(2-4):285-96.
A potent LH-RH antagonist (Ac-D-Trp1,2, D-Cpa2, D-Lys6, D-Ala10 LH-RH (Antag) was used to study the differential regulation of FSH and LH secretion by endogenous LH-RH in ovariectomized (OVX) and regularly cycling rats. The endogenous LH-RH was suppressed by single injections of Antag in OVX animals and by long-term treatment with Antag in normal and OVX rats. Serum and pituitary LH and FSH, as well as serum estradiol (E2) and progesterone (P) was determined by RIA during and/or after the treatment. The direct effect of the antagonistic analog on the ovarian P release was tested in vitro using the isolated luteal cell system. Single injections of the Antag in OVX animals caused prompt and marked suppression of the serum LH (-80%), while no decrease of the serum FSH. Long-term treatment with the same analog decreased the serum LH by 50% but did not modify the serum FSH. In normal rats, serum LH dropped to undetectable levels, while serum FSH did not change significantly. Long-term treatment with the antagonist also resulted in divergent alterations in the pituitary gonadotropin concentrations. In OVX animals, the pituitary LH content moderately elevated (+21%), however, the FSH did not change. In normal rats, ovarian cycles were interrupted, and no ovulation appeared during the treatment. The pituitary LH concentration increased by 46%, while the FSH decreased by 43%. Marked depression was found in the serum P (-60%) but no significant change in the serum E2 levels. Incubation of isolated luteal cells with the Antag did not influence the HCG-induced P secretion in vitro, demonstrating that the in vivo inhibitory effect of the antagonistic LH-RH analog on the P secretion asserts not directly on the ovarian LH-RH receptors, but through inhibition of the endogenous LH-RH. Our studies give evidence that the long-term treatment with LH-RH antagonist suppress the LH and P but not the FSH and E2 secretion, and provide new data suggesting the presence of a FSH-releasing factor in the CNS.
一种强效促黄体生成素释放激素（LH-RH）拮抗剂（Ac-D-Trp1,2, D-Cpa2, D-Lys6, D-Ala10 LH-RH（拮抗剂））被用于研究在去卵巢（OVX）大鼠和正常周期大鼠中内源性LH-RH对促卵泡激素（FSH）和促黄体生成素（LH）分泌的差异调节。在OVX动物中，单次注射拮抗剂可抑制内源性LH-RH，在正常和OVX大鼠中，长期使用拮抗剂也可抑制内源性LH-RH。在治疗期间和/或治疗后，通过放射免疫分析法（RIA）测定血清和垂体中的LH和FSH，以及血清雌二醇（E2）和孕酮（P）。使用分离的黄体细胞系统在体外测试拮抗剂类似物对卵巢P释放的直接作用。在OVX动物中单次注射拮抗剂可迅速且显著地抑制血清LH（-80%），而血清FSH无下降。用相同类似物长期治疗可使血清LH降低50%，但未改变血清FSH。在正常大鼠中，血清LH降至无法检测的水平，而血清FSH无显著变化。长期使用拮抗剂还导致垂体促性腺激素浓度出现不同变化。在OVX动物中，垂体LH含量适度升高（+21%），然而，FSH无变化。在正常大鼠中，卵巢周期被中断，治疗期间无排卵出现。垂体LH浓度增加46%，而FSH降低43%。血清P显著降低（-60%），但血清E2水平无显著变化。用拮抗剂孵育分离的黄体细胞在体外不影响人绒毛膜促性腺激素（HCG）诱导的P分泌，表明LH-RH拮抗剂类似物在体内对P分泌的抑制作用不是直接作用于卵巢LH-RH受体，而是通过抑制内源性LH-RH。我们的研究表明，长期使用LH-RH拮抗剂可抑制LH和P的分泌，但不抑制FSH和E2的分泌，并提供了新的数据表明中枢神经系统中存在一种FSH释放因子。
