Chronic growth hormone (GH) hypersecretion induces reciprocal and reversible changes in mRNA levels from hypothalamic GH-releasing hormone and somatostatin neurons in the rat.
Effects of growth hormone (GH) hypersecretion on somatostatin-(SRIH) and GH-releasing hormone (GHRH) were studied by in situ hybridization and receptor autoradiography in rats bearing a GH-secreting tumor. 6 and 18 wk after tumor induction, animals displayed a sharp increase in body weight and GH plasma levels; pituitary GH content was reduced by 47 and 55%, while that of prolactin and thyrotropin was unchanged. At 18 wk, hypothalamic GHRH and SRIH levels had fallen by 84 and 52%, respectively. In parallel, the density of GHRH mRNA per arcuate neuron was reduced by 52 and 50% at 6 and 18 wk, while SRIH mRNA levels increased by 71 and 83% in the periventricular nucleus (with no alteration in the hilus of the dentate gyrus). The numbers of GHRH- and SRIH-synthetizing neurons in the hypothalamus were not altered in GH-hypersecreting rats. Resection of the tumor restored hypothalamic GHRH and SRIH mRNAs to control levels. GH hypersecretion did not modify 125I-SRIH binding sites on GHRH neurons. Thus, chronic GH hypersecretion affects the expression of the genes encoding for GHRH and SRIH. The effect is long lasting, not desensitizable and reversible.
Bertherat
J
J
Institut National de la Santé et de la Recherche Médicale (INSERM) U 159, Centre Paul Broca, Paris, France.
Timsit
J
J
Bluet-Pajot
M T
MT
Mercadier
J J
JJ
Gourdji
D
D
Kordon
C
C
Epelbaum
J
J
D000818:Animals; D001835:Body Weight; D005246:Feedback; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000032:analysis / Q000187:drug effects / Q000235:genetics*; D007031:Hypothalamus / Q000737:chemistry*; D017403:In Situ Hybridization; D007457:Iodine Radioisotopes; D009474:Neurons / Q000737:chemistry*; D010902:Pituitary Gland / Q000737:chemistry; D010911:Pituitary Neoplasms / Q000378:metabolism; D011388:Prolactin / Q000032:analysis; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011920:Rats, Inbred WF; D013004:Somatostatin / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000032:analysis
D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D013004:Somatostatin; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone