Testosterone Regulates 25-Hydroxycholesterol Production in Testicular Macrophages

• Published in: Biology of reproduction Vol. 67; no. 5; pp. 1435 - 1438
• Main Authors: LUKYANENKO, Yevgeniya, CHEN, Jau-Jiin, HUTSON, James C
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01-11-2002
• Subjects: Animals; Biological and medical sciences; Cell Survival - drug effects; Cells, Cultured; Cholestanetriol 26-Monooxygenase; Dactinomycin - pharmacology; Dose-Response Relationship, Drug; Feedback, Physiological; Fundamental and applied biological sciences. Psychology; Hormone metabolism and regulation; Hydroxycholesterols - metabolism; Leydig Cells - metabolism; Macrophages - drug effects; Macrophages - metabolism; Male; Mammalian male genital system; Rats; Rats, Sprague-Dawley; RNA Stability; RNA, Messenger - metabolism; Steroid Hydroxylases - genetics; Steroid Hydroxylases - metabolism; Testis - cytology; Testis - metabolism; Testosterone - metabolism; Testosterone - pharmacology; Vertebrates: reproduction; Androgen; Rat; Enzyme; Hydroxylase; Rodentia; Biosynthesis; Testicle; Gene expression; Male genital system; Leydig cell; Interstitial cell; Testosterone; Vertebrata; Regulation(control); Mammalia; Animal; Testicular hormone; Oxidoreductases; Sex steroid hormone; Macrophage
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.102.007575

Recently, we found that testicular macrophages produce 25-hydroxycholesterol (25-HC) and express 25-hydroxylase, the enzyme
that converts cholesterol to 25-HC. In addition, 25-HC may be an important paracrine factor mediating the known interactions
between macrophages and neighboring Leydig cells, because it is efficiently converted to testosterone by Leydig cells. The
purpose of the present study was to determine if testosterone can regulate the production of 25-HC in rat testicular macrophages,
representing a potential negative-feedback loop from Leydig cells. We found that expression of 25-hydroxylase mRNA and production
of 25-HC by cultured testicular macrophages were significantly inhibited by testosterone at 10 μg/ml. This dose of testosterone
did not have an effect on cell viability and did not change the rate of mRNA degradation in the presence of actinomycin D.
These studies indicate that production of 25-HC is negatively regulated by testosterone, which may be representative of a
paracrine negative-feedback loop.