Peripubertal changes in the nature of the GnRH response to alpha-adrenoceptor stimulation in vitro and their modulation by testosterone.
Adrenergic mechanisms have been widely implicated in the regulation of GnRH secretion in adult rats but their role in young animals, in which the activity of the GnRH neurones is minimal, is unclear. These experiments were done to examine the effects of alpha-adrenoceptor stimulation on the secretion in vitro of GnRH by hypothalami from immature and adult male rats. The alpha 1-adrenoceptor agonist, phenylephrine (10(-9) - 10(-7) M), stimulated release of GnRH from hypothalami from adult (200 g) and peripubertal (150 g) rats but inhibited markedly the secretion of the releasing factor from the limited stores available in hypothalami from immature (50 or 100 g) rats. The stimulatory and inhibitory responses to phenylephrine, evident in adult and younger rats respectively, were concentration-dependent and antagonized readily by the selective alpha 1-adrenoceptor antagonist, alfuzosin (10(-6) M), but not by the beta-adrenoceptor antagonist, propranolol (10(-6) M). Hypothalami from 14-day castrated adult rats, in which the serum LH was elevated and hypothalamic GnRH content reduced, responded to alpha 1-adrenoceptor stimulation in vitro, like those from immature rats, with a marked reduction in GnRH release. In contrast, hypothalami from corresponding castrates bearing testosterone implants, which maintained the hypothalamic GnRH content and serum LH and testosterone concentrations at levels similar to those of intact controls, exhibited the normal 'adult' response to phenylephrine. Studies utilizing 3H-prazosin indicated that the number (Bmax) of hypothalamic alpha 1-adrenoceptor binding sites increases at puberty but that receptor affinity (KD) is unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Leposavic
G
G
Department of Pharmacology, Charing Cross and Westminster Medical School, London, UK.
Dashwood
M R
MR
Ginsburg
J
J
Buckingham
J C
JC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D007031:Hypothalamus / Q000378:metabolism; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009919:Orchiectomy; D010656:Phenylephrine / Q000494:pharmacology; D010906:Pituitary Hormone-Releasing Hormones / Q000097:blood / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D012741:Sexual Maturation / Q000502:physiology*; D013739:Testosterone / Q000097:blood / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D010906:Pituitary Hormone-Releasing Hormones; D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D013739:Testosterone; D007986:Luteinizing Hormone; C047638:alfuzosin; D011433:Propranolol