Effects of melatonin in the mediobasal hypothalamus on the secretion of gonadotrophins in sheep: role of dopaminergic pathways. 1995

D J Tortonese, and G A Lincoln
MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, UK.

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)

UI MeSH Term Description Entries
D007033 Hypothalamus, Middle Middle portion of the hypothalamus containing the arcuate, dorsomedial, ventromedial nuclei, the TUBER CINEREUM and the PITUITARY GLAND. Hypothalamus, Medial,Intermediate Hypothalamic Region,Hypothalamic Region, Intermediate,Hypothalamic Regions, Intermediate,Intermediate Hypothalamic Regions,Medial Hypothalamus,Middle Hypothalamus,Region, Intermediate Hypothalamic,Regions, Intermediate Hypothalamic
D008297 Male Males
D008550 Melatonin A biogenic amine that is found in animals and plants. In mammals, melatonin is produced by the PINEAL GLAND. Its secretion increases in darkness and decreases during exposure to light. Melatonin is implicated in the regulation of SLEEP, mood, and REPRODUCTION. Melatonin is also an effective antioxidant.
D001971 Bromocriptine A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion. 2-Bromoergocryptine,Bromocryptin,2-Bromo-alpha-ergocryptine,2-Bromo-alpha-ergokryptine,2-Bromoergocryptine Mesylate,2-Bromoergocryptine Methanesulfonate,2-Bromoergokryptine,Bromocriptin,Bromocriptine Mesylate,CB-154,Parlodel,2 Bromo alpha ergocryptine,2 Bromo alpha ergokryptine,2 Bromoergocryptine,2 Bromoergocryptine Mesylate,2 Bromoergocryptine Methanesulfonate,2 Bromoergokryptine,CB 154,CB154,Mesylate, 2-Bromoergocryptine,Mesylate, Bromocriptine,Methanesulfonate, 2-Bromoergocryptine
D003864 Depression, Chemical The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Depression,Chemical Depressions,Depressions, Chemical
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004343 Drug Implants Small containers or pellets of a solid drug implanted in the body to achieve sustained release of the drug. Drug Implant,Drug Pellet,Pellets, Drug,Drug Pellets,Implant, Drug,Implants, Drug,Pellet, Drug
D005640 Follicle Stimulating Hormone A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. FSH (Follicle Stimulating Hormone),Follicle-Stimulating Hormone,Follitropin
D006065 Gonadotropins, Pituitary Hormones secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR) that stimulate gonadal functions in both males and females. They include FOLLICLE STIMULATING HORMONE that stimulates germ cell maturation (OOGENESIS; SPERMATOGENESIS), and LUTEINIZING HORMONE that stimulates the production of sex steroids (ESTROGENS; PROGESTERONE; ANDROGENS). Pituitary Gonadotropins
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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