Sam Brody

Ribonuclease activity and cellular growth.

Abstract 1. 1. A spectrophotometric assay for ribonuclease is described. The method is sensitive to 5 · 10 −4 μ g of crystalline pancreas RNase under the conditions described. 2. 2. With this method the RNase activity in tissue homogenates from human placentas at different developmental stages was investigated at pH 7.7. 3. 3. A positive correlation is established between the RNase activity and the growth intensity of the tissue. There is a considerable decrease in enzymic activity during the development. 4. 4. The effect of p -chloromercuribenzoate on the ability of the tissue homogenate to degrade ribonucleic acid has been studied and the results are discussed. 5. 5. The possible implications of the results bearing on the relationship between RNase activity and endocellular synthesis or degradation of PNA are discussed.

Adrenocortical steroids, bone mineral content and endometrial condition in post-menopausal women

In 23 post-menopausal women, serum levels of cortisol, unconjugated dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), testosterone, unconjugated and total oestrone and prolactin were measured before and during an ACTH test. Significant positive correlations were found between basal levels of DHA and DHAS; DHA and unconjugated oestrone; DHA and total oestrone; testosterone and total oestrone and between unconjugated and total oestrone. ACTH significantly raised the levels of the steroids but not of prolactin. Significant positive correlations were found between basal levels and ACTH induced increments in DHA; between basal DHAS and increments in DHA and between increments in DHA and DHAS. A significant negative correlation was found between basal levels and increments in cortisol. No significant correlations were found between other combinations of hormone basal levels and/or increments. Significant positive correlations were found between basal levels of DHAS and the DHA response to ACTH respectively, and trabecular bone mineral content of the distal forearm. A significant correlation was also found between bone mineral content and pre-cancerous/cancerous state of the uterine epithelium. The results are a further support to the concept of a link between adrenal androgens and bone mineral density, and do also indicate a relation to endometrial pathology. The lack of correlation between cortisol and other steroids indicate different regulatory mechanisms. Prolactin does not seem to be involved in the regulation of the adrenal androgen synthesis.

Adrenal steroids in post-menopausal women: Relation to obesity and to bone mineral content

Basal levels and ACTH-induced increments of serum 17 alpha-hydroxyprogesterone (170HP), cortisol, 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), and dehydroepiandrosterone sulphate (DHAS) were related to the degree of obesity and to trabecular bone mineral density in 29 postmenopausal women. The ACTH-induced increment of 170HP (delta 170HP) was negatively correlated to basal DHA and delta DHA. Positive correlations were found between obesity, expressed as Brocas index, and delta DHA and the delta DHA/delta 170HP ratio. Bone mineral density was positively correlated to basal DHAS, delta DHA, delta DHAS and the delta DHA/delta 170HP ratio, and negatively correlated to delta 170HP. DHA and 170HP represent a crossroad in adrenocortical steroid biosynthesis, leading to delta 5-androgens and glucocorticoids as main products. Besides age, obesity may also influence the intra-adrenal distribution between these two main steroidogenic pathways. The results suggest that differences at a very early stage of the adrenal steroidogenesis may influence calcium homeostasis in the post-menopausal woman.

Serum Sex Hormone Binding Globulin (SHBG), Testosterone/SHBG Index, Endometrial Pathology and Bone Mineral Density in Postmenopausal Women

Serum levels of sex hormone binding globulin (SHBG) and testosterone (T) and bone mineral density (BMC) in the non‐dominant forearm were determined in 28 postmenopausal women aged 44‐62 years. Significant correlations (Spearmans rank correlation test) were found between BMC and SHBG (negative) and between BMC and the T/SHBG index on biologically active androgen (positive). Significant correlations were also found between endometrial pathology (Kruskal‐Wallis test; 0 = atrophic, 1 = hyperplasia, 2 = cancer) and SHBG (negative) and the T/SHBG index (positive). It is suggested that SHBG may act as one common denominator in the pathogenesis of postmenopausal osteoporosis and endometrial disease by regulating the levels of unbound, biologically active androgens and estrogens.

Ribonuclease and desoxyribonuclease activities in normal and regenerating bone marrow homogenates.

Abstract 1. 1. Phenylhydrazine was used to induce regeneration of chicken bone marrow. 2. 2. The mitotic frequencies were determined and showed up to a 10-fold increase in the regenerating tissues. 3. 3. The pentose and desoxypentose nucleic acids were determined in the two types of tissue. A consistent increase in the PNAP/DNAP quotients was noted in the regenerating tissues. 4. 4. The ribonuclease activity in the bone marrow homogenates has its pH optimum near 7.5. A correlation between the enzymic activity and the state of growth was found. 5. 5. The desoxyribonuclease activity in the bone marrow homogenates shows a pH optimum near 5.7. The influence of magnesium at different pH values was studied. A good correlation between the desoxyribonuclease activity and the state of growth of the tissue was found. 6. 6. The relationship between the metabolism of the pentose and desoxypentose nucleic acids and the corresponding enzymic activities is discussed.

ADRENAL STEROIDS, BONE MINERAL CONTENT AND ENDOMETRIAL PATHOLOGY IN POSTMENOPAUSAL WOMEN

Abstract. In 19 postmenopausal women, basal serum levels of cortisol, unconjugated dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), testosterone and unconjugated and total estrone were measured both before and during an ACTH test. A positive correlation was found both between basal levels of DHAS and the DHA response to ACTH, respectively, and trabecular bone mineral content of the distal forearm. A significant correlation was also observed between bone mineral content and precancerous/cancerous states of the uterine epithelium.

Peripheral Hormone Levels and the Endometrial Condition in Postmenopausal Women

Abstract. Thirteen postmenopausal women with benign endometrial changes including proliferative, secretory and polypous endometrium, endometrial hyperplasia and atypia (group I) and 13 randomly selected age‐matched controls with normal atrophic endometrium (group II) were studied with respect to serum levels of dehydroepiandrosterone (DHA) and its sulfate (DHAS), testosterone, total estrone, estradiol‐17β, progesterone, FSH and prolactin. Serum levels of DHA, DHAS, testosterone and total estrone were significantly higher in group I than in group II; otherwise no significant differences Were found. Mean values for body weight and for Brocas index, respectively, were almost identical in the two groups.

Scheduled Intermittent Periods of in vitro Fertilization Treatments

Organization and results of an in vitro fertilization program at the Huddinge University Hospital are given from its beginning in August 1985: 6 months in advance a scheme is scheduled with 2 weeks open for treatment followed by free intervals of 3-4 weeks. Follicular development is stimulated with clomiphene citrate and hMG, and assessed by analyses of estradiol and LH in serum combined with ultrasound examinations. Following the administration of hCG, eggs are collected by transvesical aspiration guided by ultrasound. The ova are inseminated with about 50,000 motile spermatozoa, and cultured for 48 h. Up to four eggs are transferred transcervically to the uterine cavity. 158 egg pickups have been performed (August 1985 to December 1987) in 106 patients resulting in fourteen intrauterine and two ectopic pregnancies, biochemical pregnancies not counted. This protocol has restricted routine work load allowing these treatments to be part of the clinical routine. It has also allowed the application of research programs and thus optimized limited resources.

Hormonal influence on the phosphorylase activity of the human myometrium

Abstract The phosphorylase activity in human myometrium from women in the post-menopausal period, from non-pregnant women with ovarian function, from pregnant women at different stages of pregnancy and from women in the puerperal period has been determined. The accuracy of the determination method has been evaluated by statistical analysis, the standard deviation being 6.1% of the average. In all these different states, the phosphorylase a activity (the activity determined in the absence of added adenosine-5′-phosphate) amounts to approximately 65% of the total phosphorylase activity (the activity determined when adding AMP to the incubation mixture). This implies that practically all the measurable myometrial phosphorylase activity is present in the a form. The phosphorylase activity exhibits a considerable increase during the hormone-induced growth of the human uterus. The activity in a post-menopausal uterus is 1.8 · 10 −6 enzyme units per tissue unit and the activity at the term of pregnancy 156 · 10 −6 units per tissue unit. After parturition there is a considerable and rapid decrease in the phosphorylase activity. Four days after parturition the activity is 87 · 10 −6 units per tissue unit. It has been demonstrated that the changes in the phosphorylase activity are accompanied by changes in the average amount of glycogen per tissue unit. The possible implications of these findings in relation to the endocellular function of the enzyme are discussed.

A scheduled in vitro fertilization program at Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden

embryos were transferred per patient. Twenty-four ongoing pregnancies have been established, for a pregnancy rate of 17.1%. Nine women have delivered, including two sets of twins. Of the 143 women undergoing laparoscopy for GIFT, 41 pregnancies have been established, resulting in a clinical pregnancy rate of 29%. Two ectopic pregnancies have occurred. Sixteen pregnancies have been delivered, including four sets of twins. Our 1987 pregnancy rate is 23% for IVF and 35% for GIFT. We are currently accepting 70 couples per month into our program. Embryo cryopreservation and gamete and embryo donation are options which are also available.