The role of the mu(1) opioid receptor subtype in the regulation of prolactin and growth hormone secretion by Beta-endorphin in female rats: studies with naloxonazine

The μ opioid receptor subtype has been reported to mediate the prolactin secretory response to opioids. This receptor subtype has been implicated in the morphine-induced prolactin increase, as well as the prolactin response to μ-specific opioid peptides. Subtypes of the μ receptor have been proposed and the μ(1) , site has been postulated as the receptor subtype involved in the morphine-induced prolactin secretory response. However, the role of this receptor subtype in mediating the endocrine effects of the endogenous opioid peptides has not been characterized. In order to determine the physiological significance of this receptor subtype, animals were pretreated with saline, WIN 44,441-3 (a μ, δ and κ antagonist) or naloxonazine (a μ(1) antagonist) followed by a stimulatory dose of morphine or β-endorphin. A dose response study for β-endorphin was conducted to determine the minimal stimulatory dose of β-endorphin on the prolactin and growth hormone (GH) secretory response. The dose response study indicated that β-endorphin is a more potent stimulus for prolactin release than for GH. A dose as low as 25 ng increased prolactin levels as much as 100-fold in both lactating and diestrous female rats. In contrast, 2.5 μg β-endorphin was required in order to consistently and significantly increase circulating levels of GH by 2- to 3-fold. WIN 44,441-3 antagonized the stimulatory effects of β-endorphin on both prolactin and GH secretion. Naloxonazine pretreatment abolished the morphine-induced prolactin secretory response, without affecting the GH increase in diestrous females. Naloxonazine also antagonized the prolactin response to β-endorphin in both lactating and diestrous females. In addition, it attenuated the GH secretory response but did not totally abolish it. These data indicate that β-endorphin elicits an increase in prolactin release through an opioid specific receptor which appears to be the μ(1) opioid receptor subtype. They further suggest that β-endorphin may increase GH levels, at least partially, via its action at this μ(1) site.