title: Pharmacological regulation of the cholesterol transport machinery in steroidogenic cells of the testis.
abstract: Reduced serum testosterone (T), or hypogonadism, is estimated to affect about 5 million American men, including both aging and young men. Low serum T has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass and bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Administering exogenous T, known as T-replacement therapy (TRT), reverses many of the symptoms of low T levels. However, this treatment can result in luteinizing hormone suppression which, in turn, can lead to reduced sperm numbers and infertility, making TRT inappropriate for men who wish to father children. Additionally, TRT may result in supraphysiologic T levels, skin irritation, and T transfer to others upon contact; and there may be increased risk of prostate cancer and cardiovascular disease, particularly in aging men. Therefore, the development of alternate therapies for treating hypogonadism would be highly desirable. To do so requires greater understanding of the series of steps leading to T formation and how they are regulated, and the identification of key steps that are amenable to pharmacological modulation so as to induce T production. We review herein our current understanding of mechanisms underlying the pharmacological induction of T formation in hypogonadal testis.
authors.affiliation: The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Aghazadeh
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Zirkin
authors.affiliation: The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada; Department of Biochemistry, McGill University, Montreal, Quebec, Canada; Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada. Electronic address: vassilios.papadopoulos@mcgill.ca.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Papadopoulos
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis* / Q000378:metabolism; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D013737:Testis / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*
chemical_list: D013739:Testosterone; D002784:Cholesterol
keywords: Aging; Cholesterol transport; Hypogonadism; Infertility; Leydig cells; STAR; Steroidogenesis; TSPO; Testosterone; Testosterone replacement therapy; VDAC1