Female adipocyte androgen synthesis and the effects of insulin

Abstract

The metabolic syndrome is a cluster of metabolic disorders characterized by insulin resistance and hyperinsulinaemia, and its presence can increase the risk of cardiovascular disease significantly. The metabolic syndrome is associated with increased circulating androgen levels in women, which may originate from the ovaries and adrenal glands. Adipocytes are also able to synthesise steroid hormones, and this output has been hypothesised to increase with elevated insulin plasma concentrations. However, the contribution of the adipocytes to the circulating androgen levels in women with metabolic syndrome is limited and the effects of insulin are not fully understood. The aim of this study was to investigate the presence of steroid precursors and synthetic enzymes in human adipocyte biopsies as markers of possible adipocyte androgen synthesis. We examined pre and mature adipocytes taken from tissue biopsies of abdominal subcutaneous adipose tissue of participating women from the Department of Obstetrics and Gynaecology, of the Royal Derby Hospital. The results showed the potential for localised adipocyte androgen synthesis through the presence of the androgen precursor progesterone, as well as the steroid-converting enzyme 17α-hydroxylase. Furthermore, we found the controlled secretion of androstenedione in vitro and that insulin treatment caused levels to increase. Continued examination of a localised source of androgen production is therefore of clinical relevance due to its influence on adipocyte metabolism, its negative impact on female steroidogenic homeostasis, and the possible aggravation this may have when associated to obesity and obesity related metabolic abnormalities such as hyperinsulinaemia.

Systemic Estrone Production and Injury-Induced Sex Hormone Steroidogenesis after Severe Traumatic Brain Injury: A Prognostic Indicator of Traumatic Brain Injury-Related Mortality

“…Multiple studies have linked elevated E1 levels to obesity because of the increased aromatization occurring in adipose tissue. 70,71,74 Given that acute elevations in progesterone are a consequence of TBI 11 and that progesterone can be utilized by adipose tissue for Andro and, subsequently, E1 production, 75 it is somewhat surprising increased BMI is not associated with increased E1 production following injury. However, BMI is neither the most accurate marker for obesity nor does it accurately predict physiological consequences of increased adiposity, [76][77][78] factors which may explain this lack of association.…”

Associations of adipocytokine expression and cardiovascular risk factors in stable coronary artery disease

“…Предполагается, что половой диморфизм экспрессии лептина у людей обусловлен зависимой от эстрогеновых рецепторов стимуляцией экспрессии лептина в ЖТ эстрогенами и предшественниками эстрогенов у женщин [13]. Было показано, что уровень мРНК лептина в адипоцитах женщин не изменялся в присутствии тестостерона из-за низкой экспрессии ароматазы в адипоцитах человека по сравнению с преадипоцитами, что может быть обусловлено превращением части тестостерона в эстрогены путём ароматизации [14].…”

Androgen-induced epigenetic modulations in the ovary

“…In the last few years, there has been much focus on understanding androgen actions in women and androgens have emerged as a critical regulator of follicular development and female fertility (Prizant et al 2014, Walters 2015 in both normal and pathophysiological conditions. In women, androgens are produced in the ovaries (Franks & Hardy 2018), adrenal glands (Burger 2002), and fat cells (Cadagan et al 2014) which exhibit its actions directly through androgen receptors (AR). In female reproduction, high levels of androgens have been considered detrimental to women's health leading to polycystic ovary syndrome (PCOS), hirsutism, and metabolic dysfunctions such as abdominal visceral adiposity, insulin resistance, and metabolic disturbances (London 1987, Escobar-Morreale et al 2014.…”