gamma-MSH increases intracellular cAMP accumulation and GnRH release in vitro and LH release in vivo.
The roles of the melanocortin 3 receptor (MC3-R) and its agonist, gamma(2)-melanocyte-stimulating hormone (gamma(2)-MSH) in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis are poorly understood. Here we show gamma(2)-MSH stimulated intracellular cAMP accumulation and gonadotrophin-releasing hormone (GnRH) secretion in the immortalised GnRH cell line GT(1)-7. The MC3/4-R antagonist Agrp blocked these actions. Reverse transcriptase polymerase chain reaction demonstrated GT(1)-7 cells express MC3-R mRNA. gamma(2)-MSH also stimulated GnRH release from hypothalamic explants. In vivo, gamma(2)-MSH administration into the medial preoptic area significantly increased plasma luteinising hormone. MC3-R and gamma(2)-MSH may modulate the HPG axis.
Stanley
S A
SA
Endocrine Unit, Division of Investigative Science, ICSM, Hammersmith Hospital, Du Cane Road, W12 0NN, London, UK.
Davies
S
S
Small
C J
CJ
Gardiner
J V
JV
Ghatei
M A
MA
Smith
D M
DM
Bloom
S R
SR
D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007267:Injections; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D011301:Preoptic Area; D051381:Rats; D017208:Rats, Wistar; D044104:Receptor, Melanocortin, Type 3; D018043:Receptors, Corticotropin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000521:alpha-MSH / Q000008:administration & dosage / Q000494:pharmacology; D019825:gamma-MSH / Q000008:administration & dosage / Q000494:pharmacology*
D044104:Receptor, Melanocortin, Type 3; D018043:Receptors, Corticotropin; D019825:gamma-MSH; D007987:Gonadotropin-Releasing Hormone; D000521:alpha-MSH; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP