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 luteinizing hormone (LH), PRL and their testicular receptors (R) were studied in neonatal and adult rats. Changes in gene expression were monitored by measurements of steady-state mRNA levels. Five-day and 90-day-old 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 levels. Vehicle-treated age-matched animals served as controls. hCG suppressed serum LH in 2 days in adult rats from 0.85 +/- 0.16 to 0.04 +/- 0.01 microg/l, and in neonates from 0.59 +/- 0.29 to levels below 0.01 microg/l (p < 0.01 for both). This was accompanied at both ages by a 60% decrease in pituitary content of the LH beta-subunit mRNA (p < 0.01), but a decrease in the alpha-chain (40%, p < 0.05) occurred only in neonates. 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 animals. 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 homologous down-regulation of testicular LHR (near 100%) was accompanied in 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 accompanied 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 levels 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 testicular R levels were only partly explained by changes in steady-state levels of the respective mRNAs. In general, the autoregulatory effects on LHR and PRLR appeared to affect steady-state levels of cognate mRNAs, whereas heteroregulation predominately involved changes at the protein level. The responses of the neonatal pituitary-gonadal axis to hCG and/or BR differed greatly from those observed in the adult, indicating that the mechanisms involved in these regulatory events in adult animals are a result of gradual postnatal development.
Pakarinen
P
P
Department of Physiology, University of Turku, Finland.
Niemimaa
T
T
Huhtaniemi
I T
IT
Warren
D W
DW
D000818:Animals; D001971:Bromocriptine / Q000378:metabolism / Q000494:pharmacology*; D006063:Chorionic Gonadotropin / Q000378:metabolism / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D007986:Luteinizing Hormone / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
D006063:Chorionic Gonadotropin; D006727:Hormone Antagonists; D011974:Receptors, LH; D011981:Receptors, Prolactin; D001971:Bromocriptine; D011388:Prolactin; D007986:Luteinizing Hormone