Inhibition of pituitary bioactive prolactin secretion in the male rat by the glucocorticoid agonist decadron phosphate

Abstract

In the present studies, the soluble glucocorticoid agonist, decadron phosphate (DEC), was administered i.v. to intact adult male rats in order to evaluate the effects of glucocorticoid receptor stimulation on circulating levels of immunoreactive (ir-) and bioactive (bio-) prolactin (PRL). In light of reports that glucocorticoid-specific receptors exist within the rat brain, additional experiments investigated the effects of intracerebroventricular (i.c.v.) administration of graded doses of the same drug on pituitary ir- and bioPRL secretion. Concentrations of ir- and bioPRL in samples obtained before and after drug treatments were determined by standard PRL radioimmunoassay and the Nb2 rat node lymphoma bioassay, respectively. Rats injected i.v. with 0.5 mg DEC/kg body weight, but not those treated with a tenfold lesser dose, exhibited decreased plasma irPRL concentrations. However, both doses promoted a decline in circulating levels of bioPRL compared to vehicle- treated controls, along with an overall reduction in the plasma bio/irPRL ratio. The magnitude and duration of this drug-induced decline in biopotency of secreted hormone was dose-dependent. While the plasma bio/irPRL ratio was diminished only transiently in rats injected with 0.05 mg DEC/kg, treatment with the higher dose led to a sustained decrease in the plasma bio/irPRL ratio for the duration of the experiment. The current studies also show that intracerebral administration of DEC resulted in dose-dependent alterations in pituitary PRL release. Circulating levels of ir- and bioPRL were not altered in rats injected i.c.v. with 10 ng of DEC, the lowest dose tested. However, animals treated with 100 ng of DEC showed diminished plasma concentrations of bioPRL, while rats injected with 1.0 μg DEC exhibited decreases in circulating levels of ir- as well as bioPRL. Neither of the two larger i.c.v. doses had any significant impact on plasma bio/irPRL ratios. The present results provide evidence that glucocorticoids may modulate pituitary lactotrope function in part through inhibitory neuroendocrine mechanisms initiated within the brain, and suggest that glucocorticoid receptors may exist within neural pathways that regulate pituitary PRL secretion. Current observations of a differential modification in the plasma bio/irPRL ratio following systemic versus intracerebral administration of DEC suggest that disparate mechanisms governing the release of bioactive hormonal forms of PRL may be initiated as a result of stimulation of glucocorticoid receptors distributed systemically versus those restricted to sites within the brain.