Mats-Göran Damber

A radioimmunoassay for “the pregnancy zone protein”

Abstract A solid-phase “direct” radioimmunoassay which is highly sensitive (detecting less than 50 ng/ml) and reproducible is described for the assay of the “pregnancy zone” protein in human serum. With the described technique it was possible to measure this protein in sera from normal healthy males and females. It could also be demonstrated in amniotic fluid.

Danazol and gestagen displacement of testosterone and influence on sex-hormone-binding globulin capacity*

The mechanism of action of danazol is poorly understood, but this testosterone (T) derivate is frequently used in the clinical treatment of endometriosis, and its tendency to androgenic/anabolic side effects is well known. The interaction of danazol with T binding to sex-hormone-binding globulin (SHBG) was studied with the use of an aqueous two-phase system with polyethylene glycol (PEG) and dextran for equilibrium partition. Competitive binding studies were also performed with norethisterone (NET), d-norgestrel (d-Ng), medroxyprogesterone acetate (MPA), and tamoxifen (TMX). Danazol, d-Ng, and NET were found to exert a marked T displacing activity, while MPA and TMX had no significant effect. The low values for SHBG binding capacity that were found during danazol therapy mainly reflect occupation of binding sites by danazol and to a lesser degree a real decrease in protein concentration. It was calculated that during treatment the total SHBG capacity in serum is approximately 20 times exceeded. Therapeutic danazol serum levels are 1000 times those of normal female total T levels; and since the affinity to SHBG for danazol was found to be 1/20 that to T one should conclude an almost total occupation of binding sites. The endocrine effects of danazol might be interpreted in terms of T displacement and as a consequence of increased levels of free T during therapy.

A NEW AND SENSITIVE METHOD FOR QUANTIFYING AND COMPARING THE BIOLOGICAL POTENCY OF VARIOUS ESTROGENS IN MAN

Abstract. The serum level of an estrogen‐inducible plasma protein was followed by a radioimmunoassay in groups of women during treatment with various estrogens. After an initial increase, the mean value for the serum concentration was stable. The plateau level after six months of treatment was taken as a parameter of estrogenic potency. Eleven different hormonal preparations were compared and an estrogen index was constructed.

Free testosterone levels during danazol therapy

Danazol is a testosterone (T) derivative widely used in the clinical treatment of endometriosis. Its mechanism of action is poorly understood, but is side effects are mainly androgenic. Previously it was demonstrated that danazol can displace T from sex-hormone-binding globulin (SHBG). The binding properties of danazol to SHBG and albumin were studied with the use of labeled danazol in an aqueous two-phase equilibrium partition system. Levels of total T, SHBG, and albumin were measured in 16 women undergoing danazol treatment for endometriosis. Thereafter, free and protein-bound T levels were calculated. A marked rise in free T was found during danazol therapy as compared with pretreatment levels. The data suggest that many of the effects of danazol could be explained by increased levels of free T during treatment.

Clinical and pregnancy outcome following ectopic pregnancy; a prospective study comparing expectancy, surgery and systemic methotrexate treatment

Background. The improved possibility of an early diagnosis of ectopic pregnancy by use of serial quantitative beta‐subunit human chorionic gonadotropin hormone levels together with transvaginal ultrasound has opened up options for conservative treatment. Systemic methotrexate treatment of unruptured ectopic pregnancy has emerged as a safe and effective alternative to surgical procedures. The aim of the present study was to investigate the effectiveness of methotrexate treatment in routine clinical practice, but also to assess pregnancy outcome during a 2.5‐year follow‐up period.

Serum Levels of Total Dehydroepiandrosterone and Total Estrone in Postmenopausal Women with Special Regard to Carcinoma of the Uterine Corpus

Abstract. Serum levels of total dehydroepiandrosterone and total estrone were determined in 18 postmenopausal women with carcinoma of the uterine corpus (stage I, grade 1–3) and in 40 healthy postmenopausal women. Elevated levels of both steroids were found in the carcinoma group, for dehydroepiandrosterone 2010±195 vs. 1299±117 nM, p<0.01, and for estrone 2.38±0.24 vs. 1.36±0.11 nM, p<0.001. Dehydroepiandrosterone as well as the precursors of estrone are almost exclusively of adrenal origin in the postmenopausal woman. Thus these findings indicate a role of the adrenal cortex in the etiology of corpus carcinoma, either by providing increased levels of substrate for the peripheral synthesis of estrone or a direct action of adrenal androgens on the endometrial tissue.

An Optimized Technique for Separation of Human Decidual Leukocytes for Cellular and Molecular Analyses

PROBLEM: Human decidua contains a significant number of leukocytes, phenotypically and functionally different from peripheral blood. In vitro studies of decidual leukocytes require constant improvement of cell isolation technique in order to obtain highly purified viable and functionally active cells.

Specific binding of 17β-estradiol in the human thymus

Abstract Many observations suggest that estrogenic preparations can depress cell-mediated immune reactions. Since cell-mediated immunity is thymus-dependent, the estrogen-binding properties of human and mouse thymus tissue were studied with the use of an aqueous two-phase separation system. A high-affinity and low-capactiy estrogen binding was found in human thymus tissue from six prepubertal children of both sexes and two grown women. A similar specific binding was found in the mouse thymus and in the human, uterus. The association constant (Ka) for the binding in the human thymus was 16.01 ± 8.98 × 109M−1. The human uterus, which is known to possess estrogen receptors, had Ka values in the same range. The binding seems to be located in the reticuloepithelial cells of the thymus. Data suggest that the human thymus is a target organ for estrogens, which may influence lymphocyte function during therapy.

The Immunological Paradox of Pregnancy

Abstract. During a normal pregnancy the fetus can be regarded as a transplant inside the uterus. The reason why this transplant is not rejected is still unclear. In this work various models for this immunological paradox and recent results within the field of pregnancy immunology are discussed.

Percutaneous oestrogen therapy opposed by lynestrenol or natural progesterone - effects on circulating oestrogens, FSH, sex hormone binding globulin and pregnancy zone protein

Three groups of post-menopausal women were treated with percutaneous 17 beta-oestradiol 3 mg daily opposed by lynestrenol 5 mg or natural micronized progesterone 200 mg and 300 mg, respectively. During 6 mth of cyclic replacement oestrogen serum levels were increased corresponding to follicular phase values. The pre-treatment ratio E1/E2 was unchanged which is in contrast to oral therapy. Progesterone had a much weaker effect on FSH levels than lynestrenol. Women treated with progestogen had regular withdrawal bleedings, while the micronized progesterone was insufficient in this respect. No increase of the oestrogen-sensitive liver proteins, sex hormone binding globulin (SHBG) and pregnancy zone protein (PZP), was recorded in spite of a marked increase in circulating oestrogens.