Intrahypothalamic growth hormone feedback: from dwarfism to acromegaly in the rat.
Two different dwarf rat models with primary (dw/dw, DW) or secondary (transgenic growth retarded, WF/Tgr) GH deficiency and contrasting hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) expression were implanted sc with GC cells. These form encapsulated rat GH-secreting tumors that maintain high plasma rat GH levels for several weeks. In both strains, GC cell tumors stimulated growth and raised GHBP levels, without affecting pituitary GH content. In DW rats, GC cell implants increased SRIH expression in the periventricular nucleus (PeV), but not in the arcuate nucleus (ARC), whereas their high GHRH expression in ARC was decreased by GC cells. In contrast, GC cell implants in WF/Tgr rats had little effect on the already high SRIH expression in PeV or low GHRH expression in ARC, although they reduced SRIH expression in ARC. GC cell implants also reduced GH receptor expression in both ARC and PeV in the WF/Tgr dwarves. Thus, chronic GH overexposure stimulates rapid growth in both dwarf strains, but has differential hypothalamic effects in these models. This experimental approach now makes it possible to study the effects of pathophysiological concentrations of GH ranging from dwarfism to acromegaly in the same animal model.
Pellegrini
E
E
U-159, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Carmignac
D F
DF
Bluet-Pajot
M T
MT
Mounier
F
F
Bennett
P
P
Epelbaum
J
J
Robinson
I C
IC
D000172:Acromegaly / Q000503:physiopathology*; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics; D004392:Dwarfism / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005246:Feedback; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D019382:Human Growth Hormone / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology*; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011920:Rats, Inbred WF; D011922:Rats, Mutant Strains; D011986:Receptors, Somatotropin / Q000378:metabolism; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D013004:Somatostatin; D013007:Growth Hormone-Releasing Hormone