Effects of opiate receptor blockade on gonadotrophin secretion before and after administration of the oestrogen receptor blocker tamoxifen in eugonadal men.
Both gonadal steroids and endogenous opioid peptides (EOPs) exert an inhibitory effect on gonadotrophin secretion. It is thought that the negative feedback action of the gonadal steroids, testosterone (T) and oestradiol (E2), on the gonadotrophin secretion is mediated by EOPs. To assess the effects of EOPs and oestrogen and their interrelationship on pulsatile LH secretion we studied two groups of eugonadal men. The subjects of the first group were tested on three different occasions, firstly under basal conditions, secondly during infusion of the opiate receptor blocker naloxone (NAL) (bolus 5 mg + 2.1 mg/h for 7 h), and finally during NAL infusion after 6 weeks administration of the oestrogen receptor blocker tamoxifen (10 mg twice daily). The subjects of the second group were studied before and after 6 weeks administration of tamoxifen. NAL infusion produced a significant increase in mean serum LH levels (4.8 +/- SD 1.5 to 6.2 +/- 1.8 U/l) and LH pulse frequency (3.7 +/- 1.6 to 5.3 +/- 1.2 pulses/7 h). No change was seen in mean LH pulse amplitudes (3.5 +/- 1.5 vs 3.4 +/- 1.0 U/l). After tamoxifen administration alone there was a significant increase in mean LH level (from 5.7 +/- 1.3 to 10.1 +/- 2.4 U/l), LH pulse amplitude (from 3.8 +/- 0.9 to 4.6 +/- 0.9 U/l) and LH pulse frequency (from 4.2 +/- 1.5 to 5.8 +/- 1.7 pulses/7 h). A significant rise in mean serum LH levels was observed during NAL infusion after previous tamoxifen administration in comparison to the infusion of NAL alone (from 6.2 +/- 1.8 to 10.5 +/- 6.2 U/l). LH pulse frequency (5.3 +/- 1.2 vs 6.3 +/- 1.3 pulses/7h) and amplitude (3.4 +/- 1.0 vs 3.6 +/- 1.5 U/l) however, did not change. Mean serum LH level and LH pulse frequency after opiate receptor and oestrogen receptor blockade together did not differ from the results obtained after oestrogen receptor blockade alone. NAL however was expected not only to block opioid-mediated oestrogen action but also androgen action and therefore to have additional effect on LH secretion, whereas tamoxifen was supposed to block only oestrogen action. From these data we conclude that EOPs exert a negative feedback effect on LH secretion by slowing the GnRH pulse generator. Because there was no additional effect of opiate receptor blockade after oestrogen receptor blockade on pulsatile LH secretion we infer that androgens may be impeded in their negative feedback action in the presence of the antioestrogen tamoxifen.
Spijkstra
J J
JJ
Department of Internal Medicine, Free University Hospital, Amsterdam, The Netherlands.
Spinder
T
T
Gooren
L J
LJ
Van Kessel
H
H
D000328:Adult; D005246:Feedback; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology*; D013997:Time Factors
D011957:Receptors, Opioid; D013629:Tamoxifen; D009270:Naloxone; D007986:Luteinizing Hormone