Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
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Target Concepts:
Gene/Protein
Disease
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Query: UMLS:C0338671 (
Steroids
)
9,479
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The vertebrate pineal gland rhythmically produces melatonin, a hormone involved in regulation of several physiological and behavioral processes. Melatonin is synthesized from serotonin essentially by two enzymatic steps involving
N-acetyltransferase
(
NAT
) and hydroxyindole-O-methyltransferase activities. We have previously demonstrated the presence of melatonin binding sites in the rat testes, and an inhibitory effect of melatonin on testicular gonadotrophin-stimulated androgen production. It is unknown whether these effects are mediated by melatonin synthesized locally or by melatonin from pineal origin. To assess the potential capacity of melatonin production by the testis, we used radiolabeled precursors to measure the activities of
N-acetyltransferase
and hydroxyindole-O-methyltransferase. The production of N-acetylserotonin was time-dependent during over 10 min of incubation. Melatonin had a linear increase throughout the 30 min incubation period with S-adenosyl-L-[methyl-14C]methionine. Identities of melatonin and N-acetylserotonin were confirmed by thin-layer chromatography. The ability of the testis to synthesize melatonin during sexual maturation was also analyzed. When activity of
NAT
was expressed per mg of protein, the maximal activity was observed on day 40. In contrast, when activity of
NAT
is expressed by the testis, the amount of
NAT
increased to peak on day 40 and remained elevated through day 70. We determined that both activities were predominantly localized in interstitial cells.
NAT
activity in seminiferous tubules was substantially decreased, representing 6.4% of
NAT
activity in interstitial cells. We concluded that rat testes are capable of synthesizing melatonin due to the presence of the enzymes necessary for the transformation of serotonin to melatonin.
Steroids
1996 Feb
PMID:Melatonin in the rat testis: evidence for local synthesis. 875 Apr 34
This study investigates the effects of acute and chronic injections of the neurosteroid dehydroepiandrosterone (DHEA) and its sulfate DHEA-S on pineal gland melatonin synthesis. Pineal melatonin production and plasma melatonin levels were investigated in young (9-week-old) and old (27-month-old) male Wistar rats. DHEA or DHEA-S have been administered acutely in a single intraperitoneal injection at a dosage of 50, 250, or 500 microg per animal, or on a long-term basis, i.e., for 8 days at a dosage of 100 microg per animal, 1 h before the onset of darkness. DHEA, at a dose of 50, 250, or 500 microg per animal, administered acutely to rats had no significant effects on pineal melatonin production whatever the age of the animals. In contrast, 500 microg DHEA-S induced a significant increase in the pineal melatonin content (15% in young animals and 35% in old animals) and the activity of
N-acetyltransferase
, the rate-limiting enzyme for melatonin synthesis in the pineal gland, (40% in young animals and 20% in old animals), without altering the activity of hydroxyindole-O-methyltransferase whatever the age of the animals. At lower concentrations (50 or 250 microg) DHEA-S had no effect on pineal melatonin production regardless of the age of the rats. Chronic injection of DHEA or DHEA-S at a dose of 100 microg had no effect on pineal melatonin or NAT and HIOMT activities in the two age groups. This work shows that DHEA-S (and not DHEA) is able, at pharmacological concentrations, to stimulate melatonin production by rat pineal glands regardless of the age of the animals.
Steroids
2004 May
PMID:Ex vivo studies on the acute and chronic effects of DHEA and DHEA-sulfate on melatonin synthesis in young- and old-rat pineal glands. 1521 12