Agonists of endogenous opioid peptides suppress LH, and stimulate cortisol and growth hormone during the follicular phase in heifers.

We evaluated the effects of [D-Ala2,Me,Phe4,Met(0)ol]-enkephalin (FK 33-824) and morphine, opioid receptor agonists, on concentrations of LH, cortisol and GH during the follicular phase in heifers. During three trials, oestrous cycles of Angus heifers were synchronized by two injections of prostaglandin F2 alpha (PGF2 alpha) resulting in 17 induced follicular phases over an 80-day period. Treatments were administered 24 h after the second injection of PGF2 alpha. Blood samples were collected at 15-min intervals from 3 h before until 5 h after i.v. administration of 2 ml physiological saline (trials 1, 2 and 3), 0.5 mg morphine/kg (trials 1 and 2) or 1.8 micrograms FK 33-824/kg (trials 1 and 2) or 6.7 micrograms FK 33-824/kg (trial 3). Administration of both doses of FK 33-824 and morphine inhibited episodic release of LH for approximately 60 min. The concentration of cortisol was increased (P less than 0.05) after both doses of FK 33-824, but was unaffected (P greater than 0.5) by morphine or saline. The serum concentration of GH was increased (P less than 0.01) after both doses of FK 33-824 or morphine, but saline was without effect. These results provide evidence of an inhibitory effect of opioid receptor agonists on LH (FK 33-824 and morphine) and a stimulatory effect on cortisol (FK 33-824) and GH (FK 33-824 and morphine) during the follicular phase in heifers. Divergent effects of morphine and FK 33-824 on cortisol observed in this study provide evidence that opioid-induced changes in LH, GH and cortisol result from activation of different opioid receptors.