Noradrenergic control of GnRH release from the ewe hypothalamus in vitro: sensitivity to oestradiol.
The present study investigates the influence of alpha(1)-adrenoreceptors in GnRH release in vitro and determines whether oestradiol modulates alpha(1)-adrenoreceptor-GnRH interaction. Within 10 min after ewe sacrifice, saggital midline hypothalamic slices were dissected, placed in oxygenated Minimum Essential Media-alpha (MEM-alpha) at 4 degrees C and within 2 h were singly perifused at 37 degrees C with oxygenated MEM-alpha (pH 7.4; flow rate 0.15 ml/min), either with or without oestradiol (24 pg/ml). After 4-h equilibration, 10-min fractions were collected for 4 h interposed with a 10-min exposure at 60 min to specific alpha(1)-adrenoreceptor agonist (methoxamine) or antagonist (thymoxamine) at various doses (0.1-10 mm). The alpha(1)-adrenoreceptor agonist (10 mm) increased (p < 0.05) GnRH release at 90 min both in presence and absence of oestradiol. However, in presence of oestradiol, alpha(1)-adrenoreceptor agonist (10 mm)-induced GnRH release remained elevated (p < 0.05) for at least 60 min. The bioactivity of the released GnRH was studied using a hypothalamus-pituitary sequential double-chamber perifusion. Only after exposure of hypothalamic slices to alpha(1)-adrenoreceptor agonist (10 mm), did the hypothalamic eluate stimulate LH release from pituitary fragments (n = 9, 7.8 +/- 12.3-36.2 +/- 21.6 ng/ml) confirming that the alpha(1)-adrenoreceptor agonist stimulated release of biologically active GnRH. In summary, GnRH release from the hypothalamus is under stimulatory noradrenergic control and this is potentiated in the presence of oestradiol.
Ghuman
S P S
SP
Department of Veterinary Clinical Science, University of Liverpool, Wirral, UK. ghuman_s@yahoo.co.in
Jones
D N
DN
Prabhakar
S
S
Smith
R F
RF
Dobson
H
H
D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008729:Methoxamine / Q000494:pharmacology; D013948:Moxisylyte / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012756:Sheep / Q000502:physiology*; D046509:Tissue Culture Techniques / Q000662:veterinary
D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D008729:Methoxamine; D013948:Moxisylyte