Differential secretion of pro-opiomelanocortin peptides by the pars distalis and pars intermedia of beagle dogs

ABSTRACT Beagle dogs were given saline, insulin or the dopamine antagonist, haloperidol, to examine peripheral concentrations of immunoreactive (ir)-pro-opiomelanocortin (POMC) peptides resulting from pars distalis or pars intermedia stimulation. Six beagles were given each test substance on separate occasions with and without dexamethasone pretreatment. Plasma was assayed directly for glucose, ir-ACTH, ir-α-MSH, cortisol and, after Sephadex G-50 Fine gel filtration chromatography, for ir-β-lipotrophin (ir-β-LPH) and ir-β-endorphin (ir-β-END) content. Injection of 0·5 units insulin/kg lowered (P < 0·001) plasma glucose from 4·9 ± 0·3 mmol/l (mean ± s.d., saline controls) to 2·3 ± 0·5 mmol/l, coincident with increasing ir-ACTH (9·5 ± 3·1 to 106 ± 54 pmol/l), cortisol (52 ± 27 to 221± 27 nmol/l), ir-β-LPH (not detectable to 34 ± 18 pmol/l) and ir-β-END (not detectable to 52 ± 22 pmol/l). Plasma ir-α-MSH concentrations were not affected by insulin. Pretreatment with dexamethasone abolished the ir-ACTH, cortisol, ir-β-LPH and ir-β-END increases in response to 0·75 units insulin/kg. Haloperidol (1 mg/kg) increased (P < 0·01) plasma ir-ACTH (to 103 ± 63 pmol/l), cortisol (to 243 ± 11 nmol/l), ir-β-LPH (to 16 ± 6 pmol/l), ir-β-END (to 136 ± 73 pmol/l) and additionally raised ir-α-MSH (7 ± 8 pmol/l in saline controls to 131 ± 80 pmol/l after haloperidol). Pretreatment with dexamethasone significantly (P < 0·01 ) reduced the plasma ir-ACTH (96%), cortisol (93%), ir-β-LPH (100%) and ir-β-END (55%) response to haloperidol, but the ir-α-MSH increase (117 ± 81 pmol/l) was not affected. The pituitary distribution of ir-β-END-like peptides was determined in tissue obtained from one healthy mongrel dog. Following G-50 gel filtration chromatography of HCl extracts, 40% of the total immunoreactivity determined in an extract of pars distalis eluted near the position of human β-LPH while 60% eluted near human β-END(1–31). In contrast, over 95% of ir-β-END eluted near β-END(1–31) in the tissue extract prepared from the neurointermediate lobe. From the in-vivo data, it appears that insulin-induced hypoglycaemia selectively activates POMC peptide secretion by the pars distalis in dogs and that this effect is totally suppressible by dexamethasone. In contrast, haloperidol appears to activate secretion of POMC peptide from both the pars distalis and pars intermedia. The dog pars distalis secretes a mixture of ir-β-LPH and ir-β-END while the pars intermedia preferentially secretes ir-β-END. J. Endocr. (1988) 117, 91–96