Effect of retinoic acid deficiency on in vivo and in vitro GH responses to GHRH in male rats.
Retinoic acid has recently been shown to increase growth hormone (GH)-gene transcription rate and GH synthesis in vitro. To investigate the role retinoic acid plays in the neuroregulation of GH secretion we have studied GH responses to growth hormone-releasing hormone (GHRH) in retinoic acid-deficient rats. Compared to normally fed male rats, retinoic acid-deficient rats showed a marked impairment in body weight, which was statistically significant after 3 weeks and maximal after 5-6 weeks (p less than 0.001). Yet, in vivo GH responses to different doses of GHRH (1, 5 and 25 micrograms/kg) in pentobarbital-anesthesized rats were similar in both groups. Also, in vitro GH responses to GHRH, forskolin, and KCl were similar in perfused pituitary cells taken from control and retinoic acid-deficient rats. However, further studies carried out in freely-moving rats showed the typical GH secretory pattern usually found in male rats of the control group, while retinoic acid-deficient rats displayed a highly variable GH secretory pattern with GH peaks of much lower amplitude. Finally, after gel electrophoresis of in vitro 35S-labelled proteins, no differences were observed in the molecular forms of GH. Considering these findings on normal pituitary responsiveness and alterations in GH pulsatility, our data suggest that retinoic acid deficiency leads to an alteration in the neuroregulation of GH secretion at the central level.
Mallo
F
F
Department of Physiology, Faculty of Medicine, University of Santiago, Santiago de Compostela, Spain.
Lamas
J A
JA
Casanueva
F F
FF
Dieguez
C
C
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014212:Tretinoin / Q000378:metabolism*
D014212:Tretinoin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone