Melatonin participates in the control of testosterone secretion from rat testis: an overview of our experience.
The androgen milieu plays an important role in the control of immunity, and melatonin (MLT) is known to modulate the immune response as well. Our recent studies have focused on the role of MLT in controlling androgen secretion from rat testis. The presence of MLT receptors, their modulation, and the effect of MLT on steroidogenesis have been studied on Percoll-purified rat Leydig cells (LCs) cultured in vitro. MLT receptors present in adult rat LCs (B(max) = 46.7 +/- 3.5 fmol/mg protein; K(d) = 88.7 +/- 6.2 pmol/l) are coupled through a pertussis toxin-sensitive G-protein and are downregulated by prolonged exposure to MLT itself. When acutely added for three hours, MLT (0.4-400 nM) inhibits T secretion in response to LH, forskolin, and GnRH, but sensitizes cAMP-dependent T secretion when present in the preincubation media (16 h). The acute inhibition of adenylyl cyclase and the block of 17-20-desmolase (with increased 17-OH-progesterone) and of calcium release from the intracellular stores, followed by sensitization of the adenylyl cyclase activity in the long term, are described as mechanisms of MLT action. Ultimately, our studies suggest that MLT is likely to control the immune response not only through its direct effects, but also by finely modulating the androgen milieu.
Dipartimento di Scienze Endocrine e Metaboliche, University of Genova, Genoa, Italy.
Sandra
S
Valenti
Massimo
M
Giusti
D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000502:physiology; D000735:Androstenedione / Q000096:biosynthesis; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D015213:Neuroimmunomodulation; D037342:Pertussis Toxin; D011388:Prolactin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D044094:Receptors, Melatonin; D015290:Second Messenger Systems / Q000187:drug effects; D013739:Testosterone / Q000096:biosynthesis / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D000735:Androstenedione; D019326:17-alpha-Hydroxyprogesterone; D011388:Prolactin; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D008550:Melatonin