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Female adipocyte androgen synthesis and the effects of insulin

View Article: PubMed Central - PubMed

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.

No MeSH data available.


1A/B–5A/B matched bright fields columns from left to right. 1A/B) Immunofluorescence of leucocytes using CYP17 antibody. Human leucocytes were probed with CYP17 primary antibody acting as a negative control. Results show no CYP17 fluorescence was present. 2A/B) Immunofluorescence of Chinese hamster ovary cells (CHO). CHO cells were used as a positive control allowing the expression of CYP17 to be seen within the cytosol. 3A/B) Fluorescence shows preadipocytes probed with β-actin antibody acted as positive control of IF protocol. 4A/B) Immunofluorescence of human preadipocytes using CYP17 antibody. Fluorescence can be seen within the cytososl. 5A/B) Immunofluorescence of mature human adipocytes using CYP17 antibody. Fluorescence can also be seen within the cytososl.
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f0005: 1A/B–5A/B matched bright fields columns from left to right. 1A/B) Immunofluorescence of leucocytes using CYP17 antibody. Human leucocytes were probed with CYP17 primary antibody acting as a negative control. Results show no CYP17 fluorescence was present. 2A/B) Immunofluorescence of Chinese hamster ovary cells (CHO). CHO cells were used as a positive control allowing the expression of CYP17 to be seen within the cytosol. 3A/B) Fluorescence shows preadipocytes probed with β-actin antibody acted as positive control of IF protocol. 4A/B) Immunofluorescence of human preadipocytes using CYP17 antibody. Fluorescence can be seen within the cytososl. 5A/B) Immunofluorescence of mature human adipocytes using CYP17 antibody. Fluorescence can also be seen within the cytososl.

Mentions: Negative controls (Fig. 1A) showed no fluorescence in contrast to positive immunofluorescence detected in CHO cells for CYP17 (Fig. 1B). β-actin probing of preadipocytes was used to show fluorescence supporting the protocol used (Fig. 1C). Examination of the presence of CYP17 within pre and mature adipocytes of our human cultures showed that CYP17 was predominantly expressed within the cytoplasm with abundant perinuclear localisation (Figs. 1D/E.). Furthermore westernblott analysis of CYP17 in both pre and mature adipocytes showed significant increased expression in preadipocytes samples (see Fig. 2).


Female adipocyte androgen synthesis and the effects of insulin
1A/B–5A/B matched bright fields columns from left to right. 1A/B) Immunofluorescence of leucocytes using CYP17 antibody. Human leucocytes were probed with CYP17 primary antibody acting as a negative control. Results show no CYP17 fluorescence was present. 2A/B) Immunofluorescence of Chinese hamster ovary cells (CHO). CHO cells were used as a positive control allowing the expression of CYP17 to be seen within the cytosol. 3A/B) Fluorescence shows preadipocytes probed with β-actin antibody acted as positive control of IF protocol. 4A/B) Immunofluorescence of human preadipocytes using CYP17 antibody. Fluorescence can be seen within the cytososl. 5A/B) Immunofluorescence of mature human adipocytes using CYP17 antibody. Fluorescence can also be seen within the cytososl.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121335&req=5

f0005: 1A/B–5A/B matched bright fields columns from left to right. 1A/B) Immunofluorescence of leucocytes using CYP17 antibody. Human leucocytes were probed with CYP17 primary antibody acting as a negative control. Results show no CYP17 fluorescence was present. 2A/B) Immunofluorescence of Chinese hamster ovary cells (CHO). CHO cells were used as a positive control allowing the expression of CYP17 to be seen within the cytosol. 3A/B) Fluorescence shows preadipocytes probed with β-actin antibody acted as positive control of IF protocol. 4A/B) Immunofluorescence of human preadipocytes using CYP17 antibody. Fluorescence can be seen within the cytososl. 5A/B) Immunofluorescence of mature human adipocytes using CYP17 antibody. Fluorescence can also be seen within the cytososl.
Mentions: Negative controls (Fig. 1A) showed no fluorescence in contrast to positive immunofluorescence detected in CHO cells for CYP17 (Fig. 1B). β-actin probing of preadipocytes was used to show fluorescence supporting the protocol used (Fig. 1C). Examination of the presence of CYP17 within pre and mature adipocytes of our human cultures showed that CYP17 was predominantly expressed within the cytoplasm with abundant perinuclear localisation (Figs. 1D/E.). Furthermore westernblott analysis of CYP17 in both pre and mature adipocytes showed significant increased expression in preadipocytes samples (see Fig. 2).

View Article: PubMed Central - PubMed

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.

No MeSH data available.