Steroid hormone receptors in human preadipocytes and regional differences

Joyner, Julie Maree (1999). Steroid hormone receptors in human preadipocytes and regional differences PhD Thesis, School of Medicine, The University of Queensland.

       
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Author Joyner, Julie Maree
Thesis Title Steroid hormone receptors in human preadipocytes and regional differences
School, Centre or Institute School of Medicine
Institution The University of Queensland
Publication date 1999
Thesis type PhD Thesis
Supervisor Bryan Emmerson
Donald Cameron
Total pages 200
Collection year 1999
Language eng
Subjects 11 Medical and Health Sciences
Formatted abstract
Central obesity is a significant health risk, contributing to the development of type 2 diabetes mellitus and ischaemic heart disease. Its effects are mediated by insulin resistance, dyslipidemia and hypertension that are highly correlated with intra-abdominal fat mass. The mass of any adipose tissue depot is influenced by adipocyte size and number. Any medically significant increase in intra-abdominal fat mass involves an increase in cell number. This occurs by differentiation of preadipocytes (adipocyte precursors). Preadipocytes also replicate to maintain the stem cell pool. Steroid hormones are important regulators of regional adipose tissue deposition. The role of steroid hormones in the replication and differentiation of human preadipocytes is not clear but there is preliminary evidence to suggest that they are very important in these mechanisms. The first level of specificity for, and degree of response to, a steroid hormone is determined by the steroid hormone receptor complement of a cell.

The aim of this research was to assess human preadipocytes for the presence of steroid hormone receptors and to determine if there were regional differences in steroid hormone receptor complement.

Subcutaneous and omental (intra-abdominal) preadipocytes from males and females were each assessed for the presence of glucocorticoid receptors, androgen receptors and oestrogen receptors. Specific steroid hormone binding was assessed using whole cell binding assays. Steroid hormone receptor gene expression was screened for using reverse-transcription-polymerase chain reaction. The presence of immunoreactive protein was studied using immunoblot techniques (for the oestrogen receptor only).

Subcutaneous and omental preadipocytes from the same individual were compared for differences in steroid hormone binding, steroid hormone receptor gene expression and immunoreactive steroid receptor protein levels (oestrogen receptor only).

These studies confirmed the presence of the glucocorticoid receptor, androgen receptor and oestrogen receptor in human preadipocytes. There was a gender dimorphism in glucocorticoid receptor distribution with less glucocorticoid receptors in omental preadipocytes compared with subcutaneous preadipocytes in females while there was no difference in glucocorticoid receptor complement between subcutaneous and omental preadipocytes in males. There was a regional difference in androgen receptor complement with omental preadipocytes having a greater number of receptors than subcutaneous preadipocytes for both genders. No regional differences in oestrogen receptor complement were confirmed.
 
As glucocorticoids increase preadipocyte differentiation, the gender dimorphism in glucocorticoid receptor complement may be a mechanism for the gender difference in adipose tissue distribution. No direct effects of androgens on human preadipocytes have been documented but their presence and the regional difference in receptor complement suggests that they contribute to the regulation of regional fat distribution by some mechanism. This is the first study to show that oestrogen receptors are present in human preadipocytes, and it suggests that the oestrogen-induced replication of human preadipocytes is nuclear receptor mediated.

With the confirmation of the presence of these steroid hormone receptors and the presence of regional differences in receptor complement, further research is required to clearly elucidate the direct effects of steroid hormones on human preadipocytes. The effect of pharmacological and replacement steroid hormones on adipose tissue, and preadipocytes in particular, needs closer investigation. These findings suggest therapeutic avenues to reduce intra-abdominal obesity that could be explored in an effort to modulate this very important risk factor for type 2 diabetes mellitus and ischaemic heart disease.

The presence of these steroid hormone receptors in human preadipocytes emphasises the important but often complex interactions between steroid hormones and adipose tissue.
Keyword Steroid hormones - Receptors
Glucose - Physiological transport

Document type: Thesis
Collection: UQ Theses (RHD) - UQ staff and students only
 
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