THE PATTERN OF TESTOSTERONE REPLACEMENT INFLUENCES THE RECOVERY OF THE STIMULATORY EFFECT OF CLONIDINE ON GROWTH-HORMONE (GH) SECRETION IN ORCHIECTOMIZED RATS

It has previously been described that the growth hormone (GH) releasin g effect of clonidine (CLO), an agonist of alpha(2)-adrenoreceptors, d isappears after orchidectomy and is restored by testosterone replaceme nt when started immediately after orchidectomy. In the present experim ents, the effects of CLO on GH release was analysed in long-term (LTO; 12 weeks) and short-term (STO; 2 weeks) orchidectomized rats. In the first experiment, LTO males were implanted with silastic capsules cont aining testosterone 10 weeks after orchidectomy and killed 2 weeks lat er, 15 min after injection of CLO (150 mu g/kg) or vehicle. In the sec ond experiment, adult males were implanted with testosterone at the mo ment of orchidectomy and decapitated 2 or 12 weeks later, 15 min after vehicle or CLO administration. In addition, in order to evaluate the effects of orchidectomy and androgen replacement on a, agonists GH rel ease further, prepubertal males (21-days-old) implanted with testoster one or 5-alpha-androstane-3-alpha,17 beta diol (alpha-diol) at the mom ent of orchidectomy were killed 2 weeks later, 15 min after ketamine-x ylazine (an alpha(2) agonist) administration. Finally, 10-day-old male s (orchidectomized 72 h before) were decapitated 15 min after CLO or v ehicle administration. Our results show that: (a) LTO and STO abolishe d the stimulatory effect of clonidine on GH secretion; (b) orchidectom y also abolished the stimulatory effect of clonidine in neonatal rats and that of xylazine in prepubertal males; (c) testosterone implanted at the moment of orchidectomy prevented the loss of the CLO effect in LTO and STO, but testosterone-delayed administration in LTO was unable to restore the effectiveness of CLO inducing GH release. We conclude that orchidectomy at all ages tested abolishes GH secretion induced by alpha(2) agonists, which suggests that the functionality of alpha-adr energic receptors involved in the control of GH secretion is criticall y dependent on a permanent exposure to testosterone in males. Copyrigh t (C) 1996 Elsevier Science Ltd.