Effects of cyclosporin treatment on prolactin pulsatility in chronic hyperprolactinemic male rats.

Neuroendocrine effects of cyclosporin (CsA) have been demonstrated, but the mechanisms involved are poorly understood. This work was designed to analyse (i) if chronic CsA administration could influence the episodic secretion of prolactin in adult male rats; and (ii) the effects of the chronic administration of the drug, in adult animals with elevated plasma prolactin levels. Male rats were implanted with one anterior pituitary gland under the kidney capsule or were sham-operated, at 30 days of age. Both pituitary-grafted and sham-operated rats were injected subcutaneously with vehicle or CsA (5 micrograms/kg/day) for 9 days beginning at the 60th day of age. In pituitary-grafted male rats, mean prolactin levels, absolute prolactin pulse amplitude and mean half-life of the hormone increased, while the pulse frequency and relative amplitude of the peaks decreased, as compared with sham-operated rats. CsA administration to sham-operated rats decreased the relative pulse amplitude of prolactin but increased the mean half-life of the hormone, the pulse duration and the mean hormone levels, as compared with rats of the same group treated with vehicle. However, CsA treatment to pituitary-grafted rats decreased mean prolactin levels and the absolute amplitude of its peaks and increased the relative amplitude of its pulses, whereas all the other parameters showed no change. When considering circulating values of prolactin in plasma from the trunk blood, CsA administration was followed by changes similar to those described when mean values of the serial samples were considered. These data suggest the existence of an interrelationship between elevated circulating prolactin levels and CsA, which probably takes place at the hypothalamic level, to regulate the pulsatile pattern of prolactin secretion in male rats, although a direct effect of the drug on the ectopic gland in pituitary-grafted male rats cannot be excluded.