title: Effects of melatonin in the mediobasal hypothalamus on the secretion of gonadotrophins in sheep: role of dopaminergic pathways.
abstract: Previous studies have shown that treatment with micro-implants of melatonin in the mediobasal hypothalamus (MBH) of sexually inactive Soay rams exposed to long days induces an increase in the secretion of FSH and reactivation of the testicular axis, as normally occurs in response to short days. The current study was conducted to investigate the possible involvement of hypothalamic dopaminergic (DA) systems in this melatonin-induced effect. At 10 weeks under long days, sexually inactive Soay rams were treated in the MBH with micro-implants containing bromocriptine (DA agonist) or sulpiride (DA antagonist), given alone or in combination with melatonin, to establish whether the DA drugs would mimic or negate the effects of melatonin. All micro-implants were inserted bilaterally and left in place for 14 weeks; the study lasted a total of 28 weeks (14 weeks implant period and 14 weeks post-implant period) while the animals remained under long days. The ability of the micro-implants to release bromocriptine and sulpiride for 14 weeks was confirmed by incubating implants in vitro and testing for the presence of the compounds in the incubate using a pituitary cell bioassay. Profiles of FSH, determined in blood samples collected three times weekly, were significantly different among treatments (time x treatment interaction, P < 0.001, ANOVA). Melatonin in the MBH induced a marked increase in the concentrations of FSH during the implant period, and a decrease during the post-implant period (P < 0.001). Bromocriptine given alone in the MBH induced a decrease in the concentrations of FSH which became statistically different from the control during the post-implant period (P < 0.05). Treatment with sulpiride alone also resulted in a suppressive effect during the post-implant period (P < 0.01). When given in combination with melatonin, bromocriptine or sulpiride significantly reduced the melatonin-induced increase in the concentrations of FSH observed during the implant period (P < 0.001). The results support the view that DA pathways in the MBH play an important role in the inhibitory regulation of gonadotrophin secretion in the ram. The inhibitory effect of bromocriptine is likely to result from the direct activation of the hypothalamic DA receptors linked to GnRH neurones regulating the secretion of FSH. The apparent paradoxical inhibitory effect of sulpiride is thought to be due to enhanced gonadal steroid negative feedback resulting from blockade of the inhibitory DA pathways, as evidenced by significantly increased secretion of testosterone (P < 0.05) in the animals receiving sulpiride in combination with melatonin.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Tortonese
authors.forename: G A
authors.initials: GA
authors.lastname: Lincoln
mesh_terms: D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D003864:Depression, Chemical; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004343:Drug Implants; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D012756:Sheep / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D012880:Skin Pigmentation / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology; D013739:Testosterone / Q000097:blood / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004343:Drug Implants; D006065:Gonadotropins, Pituitary; D001971:Bromocriptine; D013739:Testosterone; D013469:Sulpiride; D005640:Follicle Stimulating Hormone; D008550:Melatonin; D004298:Dopamine