To determine whether opiates directly modulate pituitary LH secretion in vivo, morphine was administered to hypothalamo-pituitary-disconnected (HPD) ewes which were receiving exogenous pulses of GnRH. To define the steroidal background which is permissive to a morphine-induced decrease in LH secretion, ovariectomized (OVX) ewes were treated as follows in groups of four: Group 1, no implant; group 2, small 17β-estradiol (E2) (1 cm long ´ 0.33 diameter) and progesterone (P) implants; group 3, medium E2 (1 cm long ´ 0.46 diameter) and P implants, and group 4, medium E2 implants. Jugular blood samples were taken at 10-min intervals for 9 h, during which there was a 3-hour pretreatment period, a 3-hour treatment period when the sheep were given six intravenous injections of 10 mg morphine every 30 min, and a 3-hour run-off period. Morphine inhibited the mean plasma concentrations of LH and LH pulse frequency in group 3 only, and in2/4 ewes in this group LH secretion was abolished and did not return to a pulsatile mode during the 3-hour run-off sampling period. In a second experiment designed to test the pituitary action of morphine, OVX-HPD ewes were primed with medium E2 and P implants and were given hourly pulses of 250 ng GnRH intravenously. Jugular blood samples were taken around each GnRH pulse over an 8-hour period. The first three pulses served as a control sampling period, after which the sheep were treated with morphine (six intravenous injections of 10 mg morphine every 30 min). Samples were taken over three pulses during treatment and over two more GnRH pulses after morphine. Morphine did not affect LH pulse amplitude in these steroid-primed OVX-HPD ewes. To determine whether or not sheep pituitary gland possesses opiate receptors, we performed in vitro binding studies using3H-naloxone as a ligand. Whereas appreciable specific binding (160-184 fmol/mg protein) was obtained with hypothalamic membranes, no specific binding could be demonstrated in anterior pituitary gland membranes (n = 2). These results show that morphine can inhibit LH secretion in OVX ewes, given E2 and P replacement. Furthermore, it appears that opiates act at a suprahypophyseal site to modulate LH secretion so that the anterior pituitary responds to changes in the GnRH secretory patterns. There is no direct pituitary action of morphine on LH secretion in vivo, and no specific opiate binding in the anterior pituitary gland.
- Luteinizing hormone