TRANSCRIPTIONAL AND TRANSLATIONAL REGULATION OF LH, PROLACTIN AND THEIR TESTICULAR RECEPTORS BY HCG AND BROMOCRIPTINE TREATMENTS IN ADULT AND NEONATAL RATS

Effects of altered gonadotropin and prolactin (PRL) secretion on lutei nizing hormone (LH), PRL and their testicular receptors (R) were studi ed in neonatal and adult rats. Changes in gene expression were monitor ed by measurements of steady-state mRNA levels. Five-day and 90-day-ol d male rats received a single s.c. injection of hCG (600 IU/kg), 1 mg/ kg bromocriptine (BR) twice daily, or their combination. After 2 or 8 days, the responses of LH, PRL, their testicular R, and testosterone ( T) were assessed, including measurements of the appropriate mRNA level s. Vehicle-treated age-matched animals served as controls. hCG suppres sed serum LH in 2 days in adult rats from 0.85 +/- 0.16 to 0.04 +/- 0. 01 mu g/l, and in neonates from 0.59 +/- 0.29 to levels below 0.01 mu g/l (p < 0.01 for both). This was accompanied at both ages by a 60% de crease in pituitary content of the LH P-subunit mRh.A (p < 0.01), but a decrease in the alpha-chain (40%, p < 0.05) occurred only in neonate s. hCG increased serum PRL in adult rats in 8 days over 2-fold (p < 0. 01); this did not occur in neonates. In neonates, BR increased the LH subunit mRNAs 2-fold in 8 days (p < 0.01) without a concomitant effect on serum LH; no BR effects on the LH parameters were seen in adult an imals. BR decreased pituitary PRL protein and mRNA levels at both ages (p < 0.01-0.05), but serum PRL decreased only in the adults. The homo logous down-regulation of testicular LHR (near 100%) was accompanied i n adults by a 30% decrease in LHR mRNA (p < 0.05). Also BR at this age decreased LHR binding (75% in 8 days, p < 0.01), but in this case no change occurred in the cognate mRNA. hCG and BR slightly up-regulated in adults PRLR binding, but only the 2-day effect of BR was accompanie d by a 60% increase in PRLR mRNA (p < 0:05). In neonates, both hCG and BR increased testicular LHR and PRLR mRNA levels (p < 0.01-0.05). In adult animals, both hCG and BR suppressed testicular and serum T level s after 8 days (40-70%, p < 0.01-0.05); only BR was inhibitory to T by 8 days in the neonates (p < 0.05). In conclusion, the homologous and heterologous regulatory effects of hCG and BR on LH, PRL and their tes ticular R levels were only partly explained by changes in steady-state levels of the respective mRNAs. In general, the autoregulatory effect s on LHR and PRLR appeared to affect steady-state levels of cognate mR NAs, whereas heteroregulation predominately involved changes at the pr otein level. The responses of the neonatal pituitary-gonadal axis to h CG and/or BR differed greatly from those observed in the adult, indica ting that the mechanisms involved in these regulatory events in adult animals are a result of gradual postnatal development.