No abstract

Following previous observations of the potent antifertility effects of acute treatment with LHRH or its agonistic analogs in male and female rats, this study describes the effect of long term (up to 12 weeks) treatment with an LHRH agonist, [D-Ala6, des-Gly-NH210]LHRH ethylamide (LHRH-A), on testicular and ovarian gonadotropin receptor levels and function in the rat. Treatment of adult male rats with 100 ng LHRH-A every third day led to a progressive decrease of testis, seminal vesicle, and prostate weight up to 12 weeks of treatment, while the inhibitory effect (70%) on LH receptor levels was already maximal at 1 week. When adult female rats were injected daily with 5 microgram LHRH-A for 12 weeks, ovarian LH, FSH, and PRL receptor levels were reduced 50--90%, while plasma estradiol and progesterone levels were inhibited 60% (compared with diestrus day 1). The effect of chronic administration of a low dose (5 IU) of hCG in the male rat was transient. By contrast, no sign of resistance developed up to 12 weeks of treatment with the LHRH agonist in either male or female animals.

Treatment of adult male rats with the potent LHRH agonists [D‐Leu6, des‐Gly‐NH210]LHRH ethylamide or [D‐Ala6. des‐Gly‐NH210]LHRH ethylamide led to a marked reduction of testicular LH and prolactin receptor levels accompanied by decreased plasma testosterone levels and testis, seminal vesicle and prostate weight. Maximal inhibitory effects were seen at a dose of 50 ng. After a single injection, maximal inhibitory effects were seen at 2–4 days with return toward normal levels at later time intervals. Similar results were obtained with LHRH itself although 5 μg was required for maximal effects. When the LHRH analog was administered twice a week at the 100 ng dose, degenerative signs appeared in the seminiferous tubules after one week while at four weeks, degenerative changes were so advanced that almost all germ cells had disappeared leaving only Sertoli cells.

Injection of male rats with 40-200 ng of [D-Leu6, des-Gly-NH2(10)]LHRH ethylamide for 7 days caused a maximal 80% reduction of testicular LH/hCG receptor level with one injection per day being as efficient as 3 daily injections. A similar inhibitory effect was observed on testicular PRL receptors. Testis and seminal vesicle weight as well as plasma testosterone levels were also significantly reduced by this treatment. These data indicate that a LHRH agonist, when given at a relatively low dose, is capable of reducing testicular LH/hCG and PRL receptor levels as well as testicular function, the effect being probably mediated by increased endogenous gonadotropin secretion.