Effect of carbamates on mRNA encoding lipid enzymes in hamster flank organs.
Flank organs are an androgen-dependent pilosebaceous complex present in male and female hamsters. These organs have been used for the evaluation of antiandrogenic drugs, which could be used for the treatment of androgen-dependent afflictions. This study demonstrated the role of four different steroidal carbamates 7-10 in the expression of mRNAs coding for different enzymes involved in the lipid metabolism in flank organs. To determine the biological effects of compounds 7-10 on the expression of mRNA coding for lipid enzymes, steroids 7-10, testosterone (T), progesterone (P), and/or 7-10 were applied on the flank organs. Later, the mRNA expression for the enzymes was determined by polymerase chain reaction. The binding of 8 and 9 to the progesterone receptor (PR) as well as their effects on the activity of 5α-reductase were also evaluated. Treatments with T, P, and 7-10 increased the mRNA expression for glycerol 3-phosphate acyl transferase (GPAT), β-hydroxy-β-methylglutaryl-CoA synthase (HMG-CoA-S), β-hydroxy-β-methylglutaryl-CoA reductase (HMG-CoA-R), phosphatidylinositol synthase (PI-S), and squalene-synthase (SQ-S). However, the combined treatments with P + 7-10 decreased the expression of GPAT, HMG-CoA-S, and HMG-CoA-R. Expression of mRNA for all enzymes was variable under treatment with T + 7-10. Data showed that these carbamates did not bind to the PR, but inhibited the activity of 5α-reductase. Carbamates 7-10 changed the mRNA expression model induced by T and P in flank organs.
Faculty of Sciences, Department of Pharmacy, National University of Colombia, Bogotá, Colombia.
Juan C
JC
López-Lezama
Marisa
M
Cabeza
Israel
I
Mayorga
Juan
J
Soriano
Teresita
T
Sainz
Eugene
E
Bratoeff
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase / Q000235:genetics; D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology*; D006224:Cricetinae; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000235:genetics; D005260:Female; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D008297:Male; D008647:Mesocricetus; D015394:Molecular Structure; D010052:Ovariectomy; D011467:Prostate / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D011980:Receptors, Progesterone / Q000378:metabolism; D012627:Sebaceous Glands / Q000187:drug effects* / Q000201:enzymology*; D012867:Skin / Q000187:drug effects / Q000201:enzymology; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology*
D002219:Carbamates; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D013256:Steroids; D006903:Hydroxymethylglutaryl CoA Reductases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D005992:Glycerol-3-Phosphate O-Acyltransferase; D013186:Farnesyl-Diphosphate Farnesyltransferase; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase
Acne; Flank organs; Inhibitors of 5α-reductase; Progesterone receptors; Steroidal carbamates