MOLECULAR MECHANISM FOR THE CONTROL OF AROMATASE IN MEN

Project: Research project

Description

The purpose of this project is to investigate the factors which regulate
aromatase activity in order to better understand the physiology and
pathology of male sexual development. The previously proposed role of
estrogens in the pathogenesis of male pseudohermaphroditism, pubertal
gynecomastia, benign prostatic hypertrophy, and male infertility underline
the importance of studying the regulation of estrogen production. More
than 80% of the circulating estrogens in normal men is derived from
conversion of androgens by aromatase in extraglandular tissues. Although
in vivo studies provide considerable information about the kinetics of
aromatization, cell culture of tissues that are important sites of
aromatization provides a unique opportunity for the study of factor which
regulate the enzyme. Hence, other workers have focused on the aromatase in
fibroblasts derived from adipose tissue. Recent studies in our laboratory
demonstrted that the kinetics of aromatase in skin and adipose tissue
fibroblasts were similar, suggesting that skin contributes to the total
production of estrogens in men. Furthermore, our studies demonstrated that
the regulation of aromatase in skin fibroblasts is somewhat different from
from that previously described for adipose tissue cells. Therefore, the
investigation of the regulation of aromatase in human skin fibroblasts
grown in cell culture should provide new and valuable insights regarding
the control of this enzyme. The purpose of this application will first be to define the factors which
modulate baseline aromatase activity: site of skin biopsy, age of donor,
plating density and passage number. Then, we will exlore the molecular
mechanisms responsible for two patterns of regulation that we recently
observed; the biphasic change in aromatase activity following
glucocorticoid stimulation and the suppressive effects of androgens. In
addition, we will compare the effects of cAMP and of steroid hormones on
aromatase activity. Finally, we plan to investigate the factors
responsible for the elevated levels of aromatase activity of skin
fibroblasts derived from the members of an unusual kindred with familial
gynecomastia due to elevated extra-glandular aromatase activity. Attempts
will be made to determine the genetic transmission of this trait by
studying clonal cell populations.
StatusFinished
Effective start/end date4/1/853/31/89

Funding

  • National Institutes of Health

Fingerprint

Aromatase
Skin
Estrogens
Androgens
Adipose Tissue
Cell Culture Techniques
XY Disorders of Sex Development 46
Sexual Development
Male Infertility
Prostatic Hyperplasia
Enzymes
Fibroblasts
Steroids
Tissue Donors
Hormones
Biopsy

ASJC

  • Medicine(all)