TY - CHAP
T1 - Pharmacological Regulation of the Cholesterol Transport Machinery in Steroidogenic Cells of the Testis
AU - Aghazadeh, Yasaman
AU - Zirkin, Barry R.
AU - Papadopoulos, Vassilios
N1 - Funding Information:
This work was supported by grants from the Canadian Institutes of Health Research (MOP102647 and 125983), the National Institutes of Health (R37 AG21092) to B. Z., and a Canada Research Chair in Biochemical Pharmacology to V. P. Y. A. was supported in part by predoctoral fellowships from the Research Institute of MUHC and the McGill Center for the Study of Reproduction.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Aging
KW - Cholesterol transport
KW - Hypogonadism
KW - Infertility
KW - Leydig cells
KW - STAR
KW - Steroidogenesis
KW - TSPO
KW - Testosterone
KW - Testosterone replacement therapy
KW - VDAC1
UR - http://www.scopus.com/inward/record.url?scp=84955748114&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955748114&partnerID=8YFLogxK
U2 - 10.1016/bs.vh.2014.12.006
DO - 10.1016/bs.vh.2014.12.006
M3 - Chapter
C2 - 25817870
AN - SCOPUS:84955748114
T3 - Vitamins and Hormones
SP - 189
EP - 227
BT - Vitamins and Hormones
PB - Academic Press Inc.
ER -