Maternal exposure to exogenous sex hormones in relation to birth weight of offspring

Birth weight was analyzed among singleton live births (N = 665) in Upstate New York in 1974 to women who used oral contraceptives (OC) in comparison to live births to women who used no contraceptives (N = 716), within 11 months prior to last menstrual period (LMP). In addition, birth weight was examined among live births to women who received hormone support therapy (N = 97) and hormone pregnancy tests (N = 75) during pregnancy. There was no evidence for a reduction in mean birth weight, or an increase in frequency of lower weights, among births to OC users, including those who stopped using OC within 2 months of LMP. Generally similar findings held within three maternal age groups (less than 25, 25-29, and 30-39 years). There was no evidence for a reduction in birth weight among offspring of women who received hormone pregnancy tests. Mean birth weight was relatively low among male and female births to women who received hormone therapy for "threatened abortion," but this may reflect the selection of women for such treatment rather than an effect of exogenous hormones on fetal growth.     

Cardiovascular birth defects and prenatal exposure to female sex hormones: a reevaluation of data reanalysis from a large prospective study.

In data of the U.S. Collaborative Prenatal Study (CPS), the Drug Epidemiology Unit (DEU) reported a relative risk of about 2.3 between maternal female sex hormone exposure during months 1 to 4 of pregnancy and cardiovascular malformation in infants (Heinonen et al., '77a N. Engl. J. Med., 296:67-70). Wiseman and Dodds-Smith ('84) reexamined the original CPS data and found the DEU had made errors in classification of exposure and disease of some cases. Also they challenged the classification of cases as "exposed" in those born to mothers who received the compounds outside the day 19 to 50 window of cardiovascular embryogenesis. Wiseman and Dodds-Smith stated that their reanalysis "clearly showed that there was [in the data used by the DEU] no statistically significant association between exposure in the critical organogenic period of pregnancy and cardiac malformation in offspring." They did not undertake any statistical analysis, but their reanalysis resulted in a widespread nonacceptance of the association reported by the DEU. The study reported here reclassified the cases of the original DEU study in accord with the implications of the Wiseman and Dodds-Smith reanalysis of exposure and disease. After this reclassification, an effect magnitude measure of association, the relative risk rose from 2.33 to 2.48 and remained nominally significant statistically at the .05 level. Thus, if anything, the quantitative consequences of the Wiseman and Dodds-Smith review of the data, when applied in an unbiased manner, result in an increase in the measure of effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex characteristics of neuroendocrine effects of prenatal exposure to exogenous glucocorticoids

The effects of hydrocortisone acetate treatment of rats during the last gestational week on neurochemical and morphological characteristics of the brain in early postnatal and mature offspring were studied. Disappearance of sexual differences both in aromatase and 5alpha-reductase activities and noradrenaline concentration in the preoptic area in 10-day old rats was found. Meanwhile a sexual dimorphism in serotonin metabolism emerged. In adult offspring, the prenatal exposure to glucocorticoids resulted in disappearance of sexual differences in neurocytes' nuclei volume in medial preoptic and suprachiasmatic nuclei. The adrenocortical reaction to noradrenaline infusion to the 3rd brain ventricle was absent in the experimental males and intensified in females. In males, adrenocortical reaction to restraint decreased while post-stress changes in hypothalamic noradrenaline concentration and hippocampal glutamate decarboxylase activity were not observed. In the similar experiments in females both the augmentation of adrenocortical reaction and inhibition of GABA-ergic system were revealed. The results obtained indicate the modifying effect of prenatal exposure to glucocorticoids on sexual dimorphism of neuroendocrine system.     

Effects of prenatal exposure to styrene trimers on genital organs and hormones in male rats

Styrene trimers migrate from polystyrene food container into foods. We evaluated the estrogenic activity of styrene trimers such as 2,4,6-triphenyl-1-hexene (ST-1), 1a-phenyl-4a-(1'-phenylethyl)tetralin (ST-2), 1a-phenyl-4e-(1'-phenylethyl)tetralin(ST-3), 1e-phenyl-4a-(1'-phenylethyl)tetralin (ST-4), and 1e-phenyl-4e-(1'-phenylethyl)tetralin (ST-5) using the reporter-gene assay with MVLN cells stably expressing the estrogen-stimulated reporter gene, and it was confirmed that ST-1, ST-3, and ST-4 had estrogen-like activity. On the other hand, ST-2 and ST-5 had anti-estrogen-like activity. We examined the estrogenic activity in vivo of ST-1, ST-3, and ST-4. The styrene trimers were administered to pregnant rats, and the effects on the offspring were examined. ST-1, ST-3, or ST-4 (0, 10, 100, 1000 microg/kg body wt/day) were subcutaneously injected into pregnant rats from gestational Day 11 through 17, and the male offspring were sacrificed on postnatal days (PND) 101-103. In the ST-4 treatment groups, the relative anogenital distance on PND 3 was significantly shortened. The relative testis weight was remarkably decreased in all styrene trimer treatment groups. Relative weights of the prostate and epididymides significantly decreased in the ST-4 treatment groups. The relative brain weight was markedly reduced in the ST-3 and ST-4 treatment groups. A significant decrease of the Sertoli cell count was observed in the ST-1 and ST-4 treatment groups. The serum follicle stimulating hormone level was remarkably reduced in all styrene trimer treatment groups. The luteinizing hormone level was significantly decreased and the testosterone level increased in the ST-1 and ST-4 groups. These results suggest that prenatal exposure to estrogenic styrene trimers at low levels obstructed genital organ development, and disrupted the endocrine systems of male rat offspring.     

Bone and cartilage responsiveness to sex steroid hormones.

Gonadal steroids influence the skeletal growth and metabolism both during the pubertal growth spurt and in adulthood with aging. It is now generally agreed that sex steroid effect on skeletal tissues is due to indirect and direct actions. In this presentation, in vitro effects of sex steroids on cartilage cells are reported by comparison with those observed on bone cells.     

Congenital heart disease cyanotic children

Cyanosis is often the only apparent symptom of congenital heart disease for which a child is brought to a physician. Some of the more common anomalies can be diagnosed from this and other symptoms by a general practitioner. Squatting after exertion is a sign of tetralogy of Fallot; severe disability with relatively mild cyanosis may indicate pure pulmonary stenosis. A brisk, short, rasping systolic murmur is characteristic of these conditions and of tricuspid atresia. Tetralogy of Fallot is further symptomatized by a boot-shaped heart, not greatly enlarged, and right axis deviation on electrocardiograms. Typically the lung fields are clear. The author's treatment of choice is aortic-pulmonary or subclavian-pulmonary anastomosis as indicated, preferably done after the child is three years old if the condition is not so severe as to require earlier operation. Pure pulmonary stenosis, which in some cases cannot be distinguished from tetralogy of Fallot except by cardiac catheterization and angiocardiography, may in more typical cases be diagnosed by convexity rather than concavity in the pulmonary segment and by differences in electrocardiograms. An expanding valvulotome is used to open the stenosed pulmonary valve, which is then dilated.A systolic murmur, a round heart and left axis deviation are usually found in tricuspid atresia. Shunt operations performed for relief of this condition may lead to later heart failure because of the devious rerouting of blood through the heart. The operations here outlined and others are statistically evaluated.     

Genetic association suggests that SMOC1 mediates between prenatal sex hormones and digit ratio

Men and women differ statistically in the relative lengths of their index and ring fingers; and the ratio of these lengths has been used as a biomarker for prenatal testosterone. The ratio has been correlated with a wide range of traits and conditions including prostate cancer, obesity, autism, ADHD, and sexual orientation. In a genome-wide association study of 979 healthy adults, we find that digit ratio is strongly associated with variation upstream of SMOC1 (rs4902759: P = 1.41 × 10^?8) and a meta-analysis of this and an independent study shows a probability of P = 1.5 × 10^?11. The protein encoded by SMOC1 has recently been shown to play a critical role in limb development; its expression in prostate tissue is dependent on sex hormones, and it has been implicated in the sexually dimorphic development of the gonads. We put forward the hypothesis that SMOC1 provides a link between prenatal hormone exposure and digit ratio.     

Coronary heart disease in relation to age,sex, and the menopause.

Examination of the Registrar General''s mortality data suggested that women do not lose protection from coronary heart disease (CHD) after the menopause. Apparently, at around the age of 50 men begin to lose a factor that had previously put them at increased risk of developing CHD compared with women. Male sex hormones may be risk factors for CHD, and further studies are needed to clarify their role in the aetiology of CHD in men.     

Effect of sex and prior exposure to a cafeteria diet on the distribution of sex hormones between plasma and blood cells

It is generally assumed that steroid hormones are carried in the blood free and/or bound to plasma proteins. We investigated whether blood cells were also able to bind/carry sex-related hormones: estrone, estradiol, DHEA and testosterone. Wistar male and female rats were fed a cafeteria diet for 30 days, which induced overweight. The rats were fed the standard rat diet for 15 additional days to minimize the immediate effects of excess ingested energy. Controls were always kept on standard diet. After the rats were killed, their blood was used for 1) measuring plasma hormone levels, 2) determining the binding of labeled hormones to washed red blood cells (RBC), 3) incubating whole blood with labeled hormones and determining the distribution of label between plasma and packed cells, discounting the trapped plasma volume, 4) determining free plasma hormone using labeled hormones, both through membrane ultrafiltration and dextran-charcoal removal. The results were computed individually for each rat. Cells retained up to 32% estrone, and down to 10% of testosterone, with marked differences due to sex and diet (the latter only for estrogens, not for DHEA and testosterone). Sex and diet also affected the concentrations of all hormones, with no significant diet effects for estradiol and DHEA, but with considerable interaction between both factors. Binding to RBC was non-specific for all hormones. Estrogen distribution in plasma compartments was affected by sex and diet. In conclusion: a) there is a large non-specific RBC-carried compartment for estrone, estradiol, DHEA and testosterone deeply affected by sex; b) Prior exposure to a cafeteria (hyperlipidic) diet induced hormone distribution changes, affected by sex, which hint at sex-related structural differences in RBC membranes; c) We postulate that the RBC compartment may contribute to maintain free (i.e., fully active) sex hormone levels in a way similar to plasma proteins non-specific binding.