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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.


Related in: MedlinePlus

A) Androstenedione secretion (pmol/1000 cells) by mature adipocytes after varied insulin treatment. Mature adipocyte cultures (n = 12) were grown after varied insulin treatments (1, 10, and 100 ng/ml) for 24, 48 and 86 h 3 days. Androstenedione levels were measured in conditioned media using ELISA. All measurements were compared to negative osteoclast controls and androstenedione levels found to be increased significantly (***P < 0.001) in all untreated and treated adipocyte cultures. Significance was also seen against the untreated cultures at 10 ng/ml insulin (*P < 0.05) and 100 ng/ml (**P < 0.01). B) Western blot CYP17 expression in mature adipocyte after varied insulin. Mature adipocytes were treated with varied doses of insulin in-vitro (insulin 0–100 ng/ml). Lanes were probed using CYP17a1 antibody. Exposure at 640 s shows band intensity at 59 kDa with increases in insulin. Increased CYP17 expression can be seen in adipocytes treated with 10–100 ng/ml insulin. The blot was then stripped and re probed using β-actin to control for protein loading. All blots were probed against leucocyte negative controls (not shown).
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f0015: A) Androstenedione secretion (pmol/1000 cells) by mature adipocytes after varied insulin treatment. Mature adipocyte cultures (n = 12) were grown after varied insulin treatments (1, 10, and 100 ng/ml) for 24, 48 and 86 h 3 days. Androstenedione levels were measured in conditioned media using ELISA. All measurements were compared to negative osteoclast controls and androstenedione levels found to be increased significantly (***P < 0.001) in all untreated and treated adipocyte cultures. Significance was also seen against the untreated cultures at 10 ng/ml insulin (*P < 0.05) and 100 ng/ml (**P < 0.01). B) Western blot CYP17 expression in mature adipocyte after varied insulin. Mature adipocytes were treated with varied doses of insulin in-vitro (insulin 0–100 ng/ml). Lanes were probed using CYP17a1 antibody. Exposure at 640 s shows band intensity at 59 kDa with increases in insulin. Increased CYP17 expression can be seen in adipocytes treated with 10–100 ng/ml insulin. The blot was then stripped and re probed using β-actin to control for protein loading. All blots were probed against leucocyte negative controls (not shown).

Mentions: Fig. 3 shows ELISA measurements of steroid hormone androstenedione. Examination against positive (theca cells) and negative controls (osteoclasts) showed significant levels of secretion against both 0 treatment and negative control (2.2 pmol/1000 cells).


Female adipocyte androgen synthesis and the effects of insulin
A) Androstenedione secretion (pmol/1000 cells) by mature adipocytes after varied insulin treatment. Mature adipocyte cultures (n = 12) were grown after varied insulin treatments (1, 10, and 100 ng/ml) for 24, 48 and 86 h 3 days. Androstenedione levels were measured in conditioned media using ELISA. All measurements were compared to negative osteoclast controls and androstenedione levels found to be increased significantly (***P < 0.001) in all untreated and treated adipocyte cultures. Significance was also seen against the untreated cultures at 10 ng/ml insulin (*P < 0.05) and 100 ng/ml (**P < 0.01). B) Western blot CYP17 expression in mature adipocyte after varied insulin. Mature adipocytes were treated with varied doses of insulin in-vitro (insulin 0–100 ng/ml). Lanes were probed using CYP17a1 antibody. Exposure at 640 s shows band intensity at 59 kDa with increases in insulin. Increased CYP17 expression can be seen in adipocytes treated with 10–100 ng/ml insulin. The blot was then stripped and re probed using β-actin to control for protein loading. All blots were probed against leucocyte negative controls (not shown).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0015: A) Androstenedione secretion (pmol/1000 cells) by mature adipocytes after varied insulin treatment. Mature adipocyte cultures (n = 12) were grown after varied insulin treatments (1, 10, and 100 ng/ml) for 24, 48 and 86 h 3 days. Androstenedione levels were measured in conditioned media using ELISA. All measurements were compared to negative osteoclast controls and androstenedione levels found to be increased significantly (***P < 0.001) in all untreated and treated adipocyte cultures. Significance was also seen against the untreated cultures at 10 ng/ml insulin (*P < 0.05) and 100 ng/ml (**P < 0.01). B) Western blot CYP17 expression in mature adipocyte after varied insulin. Mature adipocytes were treated with varied doses of insulin in-vitro (insulin 0–100 ng/ml). Lanes were probed using CYP17a1 antibody. Exposure at 640 s shows band intensity at 59 kDa with increases in insulin. Increased CYP17 expression can be seen in adipocytes treated with 10–100 ng/ml insulin. The blot was then stripped and re probed using β-actin to control for protein loading. All blots were probed against leucocyte negative controls (not shown).
Mentions: Fig. 3 shows ELISA measurements of steroid hormone androstenedione. Examination against positive (theca cells) and negative controls (osteoclasts) showed significant levels of secretion against both 0 treatment and negative control (2.2 pmol/1000 cells).

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 17&alpha;-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.


Related in: MedlinePlus