Feed-back effect of growth hormone on hypothalamic opioid and somatocrinin producing neurons.
Reportedly, most acromegalics are refractory to the growth hormone (GH)-releasing effect of central nervous system-acting stimuli. For instance, the synthetic analogue of met-enkephalin (Enk) viz. FK 33-824 fails to alter the high circulating GH levels of acromegalics. The most likely interpretation of such finding is that circulating GH disrupts, for a negative feedback effect, hypothalamic opioid function and/or GH-releasing hormone (GHRH) producing neurons, through which opioids exert their action. To address this issue, we have evaluated in intact and hypophysectomized male rats the effect of a high-dose GH regimen on the hypothalamic stores of endogenous opioid peptides, beta-endorphin (beta-EP) and met-enkephalin (met-enk). Moreover we have evaluated in intact male rats the effect of exogenous GH on median eminence (ME) GHRH stores and the ability of FK 33-824 to stimulate GH and prolactin (PRL) secretion and of exogenous GHRH to induce GH secretion. Human GH (25 and 250 micrograms bid for 4 days) administered to hypophysectomized rats strikingly reduced beta-EP and met-enk-like immunoreactivity (LI) in the medial basal hypothalamus, the effect being already maximal with the lower hGH dose. The higher dose of hGH diminished, though to a lower extent, hypothalamic beta EP-LI content also in intact rats, and reduced GHRH-LI content in the ME. Despite these profound biochemical alterations, the GH responsiveness to GHRH and FK 33-824 administration was preserved, while the latter drug induced a lower PRL rise in GH-treated than in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology; D004723:Endorphins / Q000096:biosynthesis*; D004744:Enkephalin, Methionine / Q000096:biosynthesis*; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology*; D013007:Growth Hormone-Releasing Hormone / Q000096:biosynthesis* / Q000494:pharmacology; D007016:Hypophysectomy; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000096:biosynthesis*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin
D004723:Endorphins; D010446:Peptide Fragments; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D011388:Prolactin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone