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Oskari Heikinheimo, Olavi Ylikorkala, Ursula Turpeinen and Pekka Lähteenmäki

Abstract.

The pharmacokinetics and metabolism of RU 486 were characterized in 17 women who received a single dose of 600 mg of RU 486 for termination of an early unwanted pregnancy. Based on the clinical outcome and serum chorionic gonadotropin values, the subjects were divided into two groups: those who aborted completely (i.e. responders; N=13) and those who did not respond to RU 486 treatment (i.e. non-responders; N = 4). The serum levels of RU 486, the monodemethylated, didemethylated and hydroxylated metabolites of RU 486 were measured by HPLC preceded by column chromatography. There were no significant differences in the serum levels of RU 486 or its metabolites between the two groups. The serum concentrations of α1-acid glycoprotein, the binding protein for RU 486, were quantitated by immunoturbidimetry. The α1-acid glycoprotein concentrations were similar in responders and non-responders. The metabolism of RU 486 was also studied by fractionating extracts of serum pools of responders and nonresponders on thin-layer chromatography, and subsequent RIA analysis of the eluates of the sliced thin-layer chromatography. Spots with similar distribution and percentages of cross-reactivity were found in both groups on the chromatography; the results were also similar to those from a serum pool to which synthetic RU 486 and its three metabolites had been added. Hence it is concluded that failure to abort in response to RU 486 therapy is not associated with altered pharmacokinetics or metabolism of RU 486.

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Tuula Pekkarinen, Ursula Turpeinen, Esa Hämäläinen, Eliisa Löyttyniemi, Henrik Alfthan and Matti J Välimäki

Objective

Concentrations of 50 and 75 nmol/l are proposed as serum 25-hydroxyvitamin D (25(OH)D) target for older people from the view of bone health. We evaluated vitamin D status of elderly Finnish women in light of these definitions, its relationship to bone mineral density (BMD) and turnover, and improvement by summer sunshine.

Design

Population-based study.

Methods

A total of 1604 ambulatory women aged 62–79 years were studied; 66% used vitamin D supplements. Serum 25(OH)D3 was measured with HPLC before and after summer, and heel BMD in spring. In subgroups, serum parathyroid hormone (PTH) and type I procollagen aminoterminal propeptide (PINP) were analyzed.

Results

In spring, 60.3% of the women had 25(OH)D3 ≤50 nmol/l, and the target of 75 nmol/l was reached by 9.1%. For supplement users, the respective numbers were 52.1 and 11.9%. Serum 25(OH)D3 did not determine BMD or bone turnover measured by serum PINP. Summer sunshine increased serum 25(OH)D3 by 17.4% (P<0.0001), but in autumn 84% of the subjects remained under the target of 75 nmol/l. In supplement users, PTH remained stable but decreased in others during summer (P=0.025).

Conclusions

Vitamin D status of elderly Finnish women is suboptimal if 25(OH)D3 levels of 50 or 75 nmol/l are used as a threshold. It is moderately increased by supplement intake and summer sunshine. However, 25(OH)D3 concentrations did not influence bone density in terms of serum PINP and bone turnover rate.

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Hanna Paatela, Feng Wang, Veera Vihma, Hanna Savolainen-Peltonen, Tomi S Mikkola, Ursula Turpeinen, Esa Hämäläinen, Matti Jauhiainen and Matti J Tikkanen

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 chromatography–tandem 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; P=0.006) and visceral (545 vs 360 pmol/kg per hour; P=0.004) adipose tissue. Visceral fat showed higher sulfatase activity than subcutaneous fat in premenopausal (P=0.035) and all (P=0.010) women. The mRNA expression levels of two estradiol-producing enzymes, aromatase and 17β-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.