Chronic activation of dopamine receptors in the female infantile rat: effect on hypophyseal hormones and on the onset of puberty.
In the female rat the period from days 7-20 of age is special with regard to regulation of hypophyseal hormone secretion. This period is characterized by high FSH levels and the occurrence of sporadic LH peaks. As it has been reported that haloperidol could enhance both gonadotropins at 12 days of age and not at later ages, it was of interest to treat rats during the infantile period with pergolide, a dopaminergic agent of long action, and evaluate its effect on hormone levels and puberty onset. Three different schedules of drug injections were applied: 1) daily injections (0.05 mg/kg.day) on days 1-10, 2) daily injections on days 5-14, and 3) daily injections on days 11-20. It was found that only animals treated with daily injections of pergolide on days 11-20 showed an advance in the age of vaginal opening and first estrus compared to distilled water-injected controls. Thus, the rest of the experiments were performed using injection schedule 3. In this group of animals serum LH and FSH levels were decreased 3 and 6 days after the beginning of pergolide treatment (13 and 16 days of age); at 19 days of age pergolide did not modify gonadotropin levels. One day after the end of pergolide treatment (day 21 of age), there was a rebound in LH levels in drug-injected rats, and a nonsignificant increment in FSH levels was observed. There were no differences in serum gonadotropin levels on days 22, 23, and 25 or peripubertally (29, 33, or 36 days of age). On the other hand, pergolide did not significantly modify PRL levels during the treatment, probably due to the already low values of PRL at these ages. Furthermore, PRL levels were not different between control and pergolide-injected rats at all other ages studied. After puberty onset, animals were observed for eight consecutive cycles, and both groups cycled regularly. Furthermore, PRL and gonadotropins levels were similar at diestrus and proestrus. To evaluate if pergolide treatment during the infantile period had caused permanent alteration in dopamine receptor sensitivity, animals were injected with haloperidol (0.1 or 0.25 mg/kg), and PRL release was evaluated. There were no differences in the hyperprolactinemic effect of the drug between groups. Finally, gonadotropin sensitivity to LHRH was similar in adult female rats in proestrus of both groups. The present results suggest that chronic activation of dopamine receptors during the infantile period evokes specific responses on gonadotropin secretion and advances the age of puberty onset.(ABSTRACT TRUNCATED AT 400 WORDS)
de Mengido
I M
IM
Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Becú-Villalobos
D
D
Díaz
G
G
Libertun
C
C
D000818:Animals; D000831:Animals, Newborn; D004334:Drug Administration Schedule; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000378:metabolism*; D010479:Pergolide / Q000008:administration & dosage / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012741:Sexual Maturation / Q000187:drug effects
D011954:Receptors, Dopamine; D010479:Pergolide; D007987:Gonadotropin-Releasing Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006220:Haloperidol