Prolactin (PRL) effects on the female reproductive system have been presumed to occur primarily at the hypothalamic-pituitary level. The following studies were designed to evaluate whether PRL can directly alter gonadotropin actions at the ovarian level. In the first experiment, 10 groups of 7 cycling adult female rats were given a daily dose of pregnant mare's serum (PMS: 25 IU) and either saline (SAL) or PRL (0.25, 0.8, 2.5, 8, or 25ug) twice daily for 4 days. In the second experiment, PMS (6 doses: 0-75 IU/d; 16 animals/dose) was administered to all animals while half the animals at each PMS dose received PRL (25ug twice daily) and half received an equal volume of diluent. Finally, hypophysectomized (hypox) adult rats (n=5-6/group) received 25 IU PMS/d and PRL (0-75 ug) twice daily. An additional group re-ceived 0 PRL and 0 PMS. Ovarian weight and histology were evaluated at the completion of each study. In the first experiment, PRL inhibited PMS-stimulated ovarian weight gain in a dose-dependent manner (p<0.01). Numbers of preantral (p<0.005) and antral (p<0.05) follicles were decreased in animals receiving an inhibitory dose of PRL (25ug BID) compared to controls. In the second experiment PRL (25 ug BID) again inhibited PMS-stimulated ovarian weight (p<0.01) at all doses of PMS. Finally, in hypox animals, PRL inhibited PMS-stimulated ovarian weight gain (25 and 75 ug PRL: p=0.001), and mean number (p<0.001) and diameter (p<0.001) of antral ovarian follicles (8-75ug PRL) compared to controls. In summary, administration of PRL inhibited PMS-stimulated ovarian weight gain, and antral follicle diameter (in hypox animals only) and number in adult female rats suggesting that in states of hyperprolactinemia, PRL alters gonadotropin-mediated activities (i.e., folliculogenesis) directly at the ovarian level in addition to its hypothalamic and pituitary actions.
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