Steroid sulfatase activity in subcutaneous and visceral adipose tissue: a comparison between pre- and postmenopausal women

Abstract

Objective: Adipose tissue is an important extragonadal site for steroid hormone biosynthesis. After menopause, estrogens are synthesized exclusively in peripheral tissues from circulating steroid precursors, of which the most abundant is dehydroepiandrosterone sulfate (DHEAS). Our aim was to study activity of steroid sulfatase, an enzyme hydrolyzing DHEAS, and expression of steroid-converting enzyme genes in subcutaneous and visceral adipose tissue derived from pre-and postmenopausal women. Design: Serum and paired abdominal subcutaneous and visceral adipose tissue samples were obtained from 18 premenopausal and seven postmenopausal women undergoing elective surgery for non-malignant reasons in Helsinki University Central Hospital. Methods: To assess steroid sulfatase activity, radiolabeled DHEAS was incubated in the presence of adipose tissue homogenate and the liberated dehydroepiandrosterone (DHEA) was measured. Gene mRNA expressions were analyzed by quantitative RT-PCR. Serum DHEAS, DHEA, and estrogen concentrations were determined by liquid chromatographytandem mass spectrometry. Results: Steroid sulfatase activity was higher in postmenopausal compared to premenopausal women in subcutaneous (median 379 vs 257 pmol/kg tissue per hour; PZ0.006) and visceral (545 vs 360 pmol/kg per hour; PZ0.004) adipose tissue. Visceral fat showed higher sulfatase activity than subcutaneous fat in premenopausal (PZ0.035) and all (PZ0.010) women. The mRNA expression levels of two estradiol-producing enzymes, aromatase and 17b-hydroxysteroid dehydrogenase type 12, were higher in postmenopausal than in premenopausal subcutaneous adipose tissue. Conclusions: Steroid sulfatase activity in adipose tissue was higher in postmenopausal than in premenopausal women suggesting that DHEAS, derived from the circulation, could be more efficiently utilized in postmenopausal adipose tissue for the formation of biologically active sex hormones.

Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results

“…Only one of 48 patients (2%) treated with palbociclib plus fulvestrant had an E2 value that was clearly premenopausal; otherwise, the values assessed for all patients were consistent with full ovarian function suppression, and there was no difference associated with the addition of palbociclib. This is supported by the significant relationship between plasma E2 levels and BMI; extragonadal estrogen production occurs mainly in subcutaneous fat [38] and resulting plasma concentrations are known to correlate with BMI [39]. Accordingly, there was no disruption of the correlation with the addition of palbociclib treatment.…”

Circulating sex steroids coregulate adipose tissue immune cell populations in healthy men

“…in pre-and postmenopausal women (65). Dissociations between serum and tissue-specific sex steroid levels also have been observed in other tissues, as clearly demonstrated by lack of associations between circulating and intraprostatic androgen levels (66,77).…”

Increased body fat mass and androgen metabolism – A twin study in healthy young women

“…The sulfate ester of DHEA is the most abundant steroid in human blood and a source of active hormones produced locally in adipose tissue [32,33]. DHEA sulfate needs to be actively transported into the cell for hydrolysis by steroid sulfatase yielding free DHEA [5].…”

“…The gene expression of steroid sulfatase (STS) was significantly upregulated in the whole subcutaneous adipose tissue and in isolated adipocytes from the heavier compared to the leaner co-twins. We have recently shown in studies in vitro that hydrolysis of both DHEA sulfate [32] and estrone sulfate [6] take place in human subcutaneous and visceral adipose tissue suggesting that increased action of steroid sulfatase might, especially in postmenopausal women, provide more precursors for local estrogen synthesis, possibly even having some impact on serum levels. In young adult women with normal ovarian sex hormone production, a Fig.…”