Effect of hypophysectomy and growth hormone replacement on hypothalamic GHRH.

Long-term (7 and 14 days) hypophysectomy resulted in a striking decrease in growth hormone releasing hormone-like immunoreactivity (GHRH-LI) in the median eminence (ME) of adult male rats, evaluated by both radioimmunoassay and immunohistochemistry. Treatment with human GH (125 micrograms/rat, twice daily IP for 14 days) prevented, though partially, depletion of GHRH-LI from the ME, as assessed by both methods. These results demonstrate that circulating GH levels regulate the function of GHRH-producing structures, via a feedback mechanism.

The beta-endorphin-induced secretion of growth hormone but not of prolactin is inhibited by an endogenous opioid antagonist.

The naturally occurring peptide human beta-endorphin-(1-27) (h beta-EP-(1-27) has been shown to antagonize beta-endorphin (h beta-EP)-induced analgesia. We have evaluated the effects of the fragment on h beta-EP-induced growth hormone (GH) and prolactin (PRL) release. It inhibited beta-EP-induced GH release in a dose-related way but left beta-EP-induced PRL stimulation unchanged.

In vivo supersensitivity of the anterior pituitary of old female rats to dopaminergic inhibition of prolactin secretion.

Old female rats (20-27 months) were given acute administration of an indirectly acting dopamine (DA) agonist, nomifensine or scalar doses of the direct DA receptor agonist, bromocriptine. Young female rats (4-9 months) were used as controls. Nomifensine (10 mg/kg i.p.) decreased significantly basal prolactin (PRL) levels in young rats as in old rats. In young rats, bromocriptine decreased significantly basal PRL levels only at the dose of 0.5 mg/kg intraperitoneally, the doses of 0.1 and 0.02 mg/kg being ineffective. In contrast, in old rats administration of 0.02 mg/kg of bromocriptine consistently inhibited basal PRL levels and the maximum PRL-lowering effect was already evident at the dose of 0.1 mg/kg. These data indicate that the pituitary of old rats, due to the age-related removal of dopaminergic inputs from the tuberoinfundibular system, becomes supersensitive to direct dopaminergic stimulation. This phenomenon may explain the normal PRL responsiveness of old rats to nomifensine, despite defective tuberoinfundibular dopaminergic function.

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)