Evidence for lactotroph dopamine resistance in idiopathic hyperprolactinemia.

Previous studies in patients with idiopathic hyperprolactinemia (IH) that have suggested the presence of decreased central dopaminergic tone have assumed normal responsiveness of lactotrophs to dopamine (DA). We have examined DA sensitivity in 17 women with IH and 19 female controls by evaluating the plasma PRL responses to successive infusions of increasing concentrations of DA (4, 40, and 400 ng/kg . min) as well as to a dopaminergic agonist, bromocriptine (2.5 mg, orally), and to a dopaminergic agonist, bromocriptine (2.5 mg, orally), and to a dopaminergic receptor blocker, domperidone (2 mg, iv). PRL levels in controls were unchanged during a saline infusion, but decreased by 34 +/- 7% (mean +/- SE) at the end of the lowest DA infusion (P less than 0.05 vs. saline). Progressive PRL suppression was produced with each increasing dose. In contrast, in patients with IH, the lowest dose produced no significant suppression from basal PRL levels (P less than 0.001 vs. controls); at 40 ng/kg . min DA, fractional suppression was evident but was less than that in controls (P less than 0.01); at 400 ng/kg . min, fractional PRL suppression in IH patients was indistinguishable from that in controls (70 +/- 6% vs. 73 +/- 4%). Patients with IH also exhibited markedly reduced and delayed PRL response to domperidone (P less than 0.02 vs. controls). Significant impairment of the PRL-lowering effect of bromocriptine was observed in the IH patients between 1 and 2 h (P less than 0.02 vs. controls), and their responses to bromocriptine were again delayed. The results indicate the presence of a relative resistance to DA in patients with IH. This resistance is compatible with a decrease in the number or affinity of lactotroph DA receptors.

Somatostatin-like immunoactivity and biological activity is present in a human pheochromocytoma.

Somatostatin (SRIF)-like immunoreactivity (SRIF-LI) has previously been demonstrated immunohistochemically in sympathetic nerves and ganglia and in adrenal medullary cells. Studies were therefore performed to determine whether SRIF-LI was present in an adrenal pheochromocytoma. Acetic cid extracts of pheochromocytoma tissue contained high SRIF-LI concentrations (5.52 micrograms/g wet wt). On Sephadex G-75 gel filtration, the major peak of pheochromocytoma SRIF-LI coeluted with synthetic SRIF. SRIF-LI of a larger molecular size was also present in the tumor. Pheochromocytoma SRIF-LI coeluted with synthetic SRIF on reverse phase high pressure liquid chromatography. Pheochromocytoma SRIF-LI purified by high pressure liquid chromatography was equipotent to synthetic SRIF in inhibiting (Bu)2cAMP-stimulated GH release by rat pituitary cells in monolayer culture. Serum SRIF-LI was elevated in the patient before surgery and was restored toward normal after removal of the tumor. Serum levels of GH, TSH, and insulin were not obviously different before and after tumor removal. The results indicate that SRIF-LI is produced in excessive quantities by a pheochromocytoma. The immunological, chromatographic, and biological properties of the pheochromocytoma SRIF-LI suggest that it is indistinguishable from synthetic SRIF. This finding extends the list of peptides produced by pheochromocytoma and may provide an additional serum marker for the tumor in man.U