Suppression of Pulsatile LH Secretion, Pituitary GnRH Receptor Content and Pituitary Responsiveness to GnRH by Hyperprolactinemia in the Male Rat

Abstract

To assess whether gonadotropin-releasing hormone (GnRH) release from the hypothalamus might be altered by hyperprolactinemia in the male rat, we measured in chronically hyperprolactinemic rats the pituitary GnRH receptor content and described the pattern of luteinizing hormone (LH) release during the postcastration rise in gonadotropin secretion 24 and 72 h after gonadectomy. In intact rats, the effect of hyperprolactinemia was determined by describing the pattern of LH secretion, pituitary GnRH receptor content and assessment of pituitary responsiveness to small doses of GnRH (1.0 ng). In addition, to determine the role endogenous opioids might play in inhibiting GnRH release in hyperprolactinemic rats, we examined the effect of both a continuous infusion and a bolus injection of the opioid antagonist naloxone on the pattern of LH release. Chronic hyperprolactinemia was achieved by implanting 4 pituitaries under the kidney capsules 3–4 weeks before study. Acute hyperprolactinemia was achieved by injecting rats with 1 mg ovine prolactin every 12 h for 3 days. Control animals were untreated or were chronically hyperprolactinemic rats in which the hyperprolactinemia was transiently reversed by treatment for 3 days with the dopamine agonist 2-α-bromoergocryptine. The mean LH concentration was greatly decreased at 24 postcastration in chronically hyperprolactinemic rats relative to controls. This decrease was associated with a decrease in LH pulse height and pulse amplitude and pituitary GnRH receptor content, but not with an increase in the LH interpulse interval. In contrast, the decrease in mean LH concentrations in hyperprolactinemic animals at 72 h postcastration was primarily associated with a significantly longer LH interpulse interval than that observed in control animals. Chronic hyperprolactinemia in intact rats decreased the pituitary GnRH receptor content, in addition to decreasing the mean LH concentrations during pulsatile GnRH administration. Chronic hyperprolactinemia also inhibited LH release relative to controls during the continuous 4-hour infusion of naloxone and in response to a bolus injection of naloxone. However, in acutely hyperprolactinemic intact male rats a bolus injection of naloxone increased LH secretion 20 min later to levels similar to those obtained in control rats. In summary, these results indicate that chronic hyperprolactinemia decreased LH secretion by primarily decreasing GnRH secretion as suggested by a decrease in pituitary GnRH receptor content and a decrease in LH pulse frequency and pulse amplitude. It is also possible that a decrease in pituitary responsiveness to GnRH may have contributed to the decrease in LH pulse amplitude. The effects of chronic hyperprolactinemia do not appear to be mediated by an opioid whose actions are antagonized by naloxone.

Lactation Alters γ-Aminobutyric Acid Neuronal Activity in the Hypothalamus and Cerebral Cortex in the Rat

“…For example, our data cannot distinguish between an effect of suckling on GABA turnover or a possible effect of PRL. There is considerable evidence that hyperprolactinemia can inhibit GnRH secretion in both male and female rats [31, 32, 33, 34]. While it is possible that the inhibitory action of prolactin could be mediated by a stimulation of hypothalamic GABAergic neurons [14, 15, 16], we have been unable to demonstrate increased GABA turnover associated with the PRL-induced suppression of postcastration LH secretion in males [21].…”

The effect of LPS on LH release and gene expression of <i>LH-β</i>, <i>GnRH-R</i> and <i>TLR4</i> in the anterior pituitary of follicular phase ewes – an <i>in vitro</i> study

“…The level of gene expression does not, however, have to directly parallel the protein level, and it can be supposed that LPS treatment decreased the amount of GnRH-R resulting in the lower sensitivity to GnRH stimulation. It is known that the reduction of GnRH-R on pituitary cells can directly lead to reduced secretion of LH (Fox et al, 1987;Nett et al, 2002;Rispoli and Nett, 2005).…”

Acute Sex Differences in Serum LH Levels in Gonadectomized Rats: Investigation of Pituitary Response to GnRH Pulse Frequency and Prolactin Secretion as Etiological Agents

“…High prolactin (PRL) levels are associated with low LH secretion in vivo [7,8] and in vitro [9]. Female pituitaries secrete much more PRL in vitro than male pituitaries [unpubl.…”