The pattern of testosterone replacement influences the recovery of the stimulatory effect of clonidine on growth hormone (GH) secretion in orchidectomized rats.

It has previously been described that the growth hormone (GH) releasing effect of clonidine (CLO), an agonist of alpha2-adrenoreceptors, disappears after orchidectomy and is restored by testosterone replacement when started immediately after orchidectomy. In the present experiments, 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 containing testosterone 10 weeks after orchidectomy and killed 2 weeks later, 15 min after injection of CLO (150 microg/kg) or vehicle. In the second experiment, adult males were implanted with testosterone at the moment 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 alpha2 agonists GH release further, prepubertal males (21-days-old) implanted with testosterone or 5-alpha-androstane-3-alpha,17beta diol (alpha-diol) at the moment of orchidectomy were killed 2 weeks later, 15 min after ketamine-xylazine (an alpha2 agonist) administration. Finally, 10-day-old males (orchidectomized 72 h before) were decapitated 15 min after CLO or vehicle administration. Our results show that: (a) LTO and STO abolished the stimulatory effect of clonidine on GH secretion; (b) orchidectomy 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 alpha2 agonists, which suggests that the functionality of alpha-adrenergic receptors involved in the control of GH secretion is critically dependent on a permanent exposure to testosterone in males.