Morphine decreases LH secretion in ovariectomized ewes only after steroid priming and not by direct pituitary action.
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 17 beta-estradiol (E2) (1 cm long x 0.33 diameter) and progesterone (P) implants; group 3, medium E2 (1 cm long x 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 in 2/4 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Horton
R J
RJ
Medical Research Centre, Prince Henry's Hospital, Melbourne, Australia.
Li
J Y
JY
Cummins
J T
JT
Smith
A I
AI
Shen
P J
PJ
Clarke
I J
IJ
D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007031:Hypothalamus / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000378:metabolism; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology*; D012756:Sheep
D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D011374:Progesterone; D004958:Estradiol; D009020:Morphine; D007986:Luteinizing Hormone