Advis J P, Richards J S, Ojeda S R
Endocrinology. 1981 Apr;108(4):1333-42. doi: 10.1210/endo-108-4-1333.
Hyperprolactinemia induced in immature female rats by treatment with sulpiride, a dopaminergic receptor blocker, increased the in vitro release of ovarian progesterone (P) in response to different doses of both highly purified hCG and human FSH. The increased P response to gonadotropins was also observed in ovaries of animals injected with ovine PRL or in rats in which the hyperprolactinemic condition was induced by pimozide, a more typical dopaminergic receptor blocker. In addition, the pimozide treatment advanced the time of puberty in a manner similar to that previously observed with sulpiride. In other experiments in which only the ovarian response to hCG, but not that to FSH, was evaluated, it was found that the in vivo treatment of hypophysectomized immature rats with sulpiride did not modify the almost undetectable serum PRL levels of these animals and failed to increase the in vitro ovarian P response to hCG. By contrast, sc injection of PRL to hypophysectomized rats clearly enhanced the in vitro release of P in response to the gonadotropin. Adrenalectomy of otherwise intact rats significantly decreased the in vitro ovarian P response to hCG and blunted the increase in the P response induced by hyperprolactinemia. These effects, however, were almost completely reversed by concomitant corticosterone replacement therapy. The ovarian content of hCG receptor in normal rats was found to increase during juvenile development (days 22-31). Hyperprolactinemic animals showed a greater ovarian hCG receptor content than age-matched 31-day-old controls. In contrast, the FSH receptor contents were similar in both groups. The increase in hCG receptor content induced by hyperprolactinemia was even more clearly manifested in isolated granulosa cells, but, as in the case of the whole ovaries, the FSH receptor content in these cells remained essentially the same in hyperprolactinemic and control rats. The results indicate that the enhanced ovarian P response to hCG induced by PRL in prepubertal rats is, at least in part, mediated by an increase in the LH receptor content of the granulosa cells of the developing follicle. It also appears that the sensitizing effect of PRL on the prepubertal ovarian P response to gonadotropins is modulated by the adrenal gland through an effect exerted by corticosterone. The mechanisms by which PRL enhances the ovarian P response to FSH do not appear to involve changes in FSH receptors. However, the occurrence of enlarged uteri in hyperprolactinemic rats suggest that the PRL-induced increase in the P response to FSH may be related to the presence of more mature, estrogen-secreting follicles resulting from the hyperprolactinemic condition.
用多巴胺能受体阻滞剂舒必利处理未成熟雌性大鼠诱导的高催乳素血症，增加了卵巢孕酮（P）对不同剂量的高度纯化人绒毛膜促性腺激素（hCG）和人促卵泡激素（FSH）的体外释放。在注射了羊催乳素（PRL）的动物卵巢中，或在用更典型的多巴胺能受体阻滞剂匹莫齐特诱导高催乳素血症的大鼠中，也观察到对促性腺激素的P反应增加。此外，匹莫齐特处理以类似于先前用舒必利观察到的方式提前了青春期时间。在其他仅评估卵巢对hCG而非对FSH反应的实验中，发现用舒必利对垂体切除的未成熟大鼠进行体内处理并未改变这些动物几乎检测不到的血清PRL水平，也未能增加卵巢对hCG的体外P反应。相比之下，对垂体切除的大鼠皮下注射PRL明显增强了对促性腺激素的P体外释放。对原本完整的大鼠进行肾上腺切除显著降低了卵巢对hCG的体外P反应，并减弱了高催乳素血症诱导的P反应增加。然而，通过同时进行皮质酮替代疗法，这些作用几乎完全逆转。发现正常大鼠卵巢中hCG受体含量在幼年发育期间（第22 - 31天）增加。高催乳素血症动物的卵巢hCG受体含量高于年龄匹配的31日龄对照。相反，两组中FSH受体含量相似。高催乳素血症诱导的hCG受体含量增加在分离的颗粒细胞中更明显地表现出来，但与整个卵巢情况一样，高催乳素血症大鼠和对照大鼠这些细胞中的FSH受体含量基本保持相同。结果表明，青春期前大鼠中PRL诱导的卵巢对hCG的P反应增强至少部分是由发育卵泡颗粒细胞中LH受体含量增加介导的。还似乎PRL对青春期前卵巢对促性腺激素的P反应的致敏作用是由肾上腺通过皮质酮发挥的作用来调节的。PRL增强卵巢对FSH的P反应的机制似乎不涉及FSH受体的变化。然而，高催乳素血症大鼠子宫增大的出现表明，PRL诱导的对FSH的P反应增加可能与高催乳素血症状态下存在更多成熟且分泌雌激素的卵泡有关。
