This study deals with the dynamic behavior of hydrocortisone in man and the relationship of the metabolic fate of this principal adrenal hormone to the physiologic or pathologic state of the experimental subject. The period during which the hormone persists in the tissues, the rate of its excretion, and the relationship between the two have been measured by precise and discriminating methods. Furthermore, the details of the metabolic transformations and the rate at which these occur have been discussed and correlated with some known biologic effects of the hormone. These studies have been possible as a result of the availability of ring A labeled hydrocortisone through a cooperative effort sponsored by the Endocrinology Study Section of the U. S. Public Health Service (1).Previous work in our laboratories employing radioactive cortisone labeled with tritium yielded information concerning the metabolites of cortisone and the routes by which they are eliminated. Exact quantitative evaluation of the total metabolites in terms of the amount given was difficult because of errors inherent in the methods employed for the analysis of tritium in very crude extracts. Other studies with C14 labeled testosterone, estrone, estradiol, progesterone, and desoxycorticosterone have been reported, and in general, these experiments showed a rapid elimination of the hormonal metabolites as conjugated substances in the urine (2). These analyses were possible 1This investigation was carried out under contract AT (30-1)-910 with the United States Atomic Energy
Exercise training improves insulin action in skeletal muscle, but the mechanisms of this effect are not completely understood. In particular, the role of the insulin receptor (IR) is unclear. We examined the IR and an enzyme indicative of oxidative capacity in muscle in relation to improved insulin action in 20 previously sedentary individuals before and after a 7-day program of moderate-intensity cycle ergometry. After training, insulin sensitivity increased 33% (6.20 +/- 0.91 vs. 8.22 +/- 1.12 min. microU(-1). ml(-1) mean +/- SE, pre- vs. posttraining, respectively, P < 0.05). The mitochondrial marker enzyme cytochrome c oxidase (COX) increased in vastus lateralis biopsies by 21% (P < 0.05). After training, IR autophosphorylation, determined by ELISA, was significantly increased by approximately 40% at insulin concentrations from 1 to 100 nM (P < 0.05). The training-induced improvements in IR autophosphorylation were significantly correlated with changes in muscle COX content (r = 0.65, P < 0.05). These studies indicate that, in this model of increased physical activity, improvements in IR function are an early adaptation to exercise in humans, are correlated with increases in muscle oxidative capacity, and likely contribute to the beneficial effects of exercise training on insulin action.
HomeoboxA10 (HOXA10) is a transcription factor that is crucial for the development and patterning of the uterus during embryogenesis. In the adult endometrium, HOXA10 expression is regulated by steroid hormones and embryonic signals. Expression of sufficient HOXA10 messenger RNA is essential to endometrial receptivity and embryo implantation. Aberrant methylation is believed to alter the expression of HOXA10. Methylation of this gene may be associated with decreased fertility, implantation defects, and/or reproductive wastage seen in certain disease states that affect the female reproductive tract. This study describes the differences in methylation patterns of HOXA10 gene in uterine myomas, endometriosis, uterine septum, Asherman syndrome, or uterine polyps of women undergoing hysteroscopic surgery. In the endometrium of uteri with polyps, submucosal myomas, and intramural myomas, there were CpG sites within the HOXA10 gene that were highly methylated compared to controls. The HOXA10 gene in women with endometriosis was hypomethylated compared to controls. DNA methylation may be a common molecular mechanism that results in reproductive dysfunction seen in gynecologic disease.
The incidence of ectopic pregnancies is increasing, which may be related to better diagnostic tools as well as the increasing use of assisted reproductive technologies. However, the signs and symptoms of ectopic pregnancy can be similar to other complications of early pregnancy such as miscarriage. Diagnosis often requires serial human chorionic gonadotropin levels along with ultrasound and, in some cases, dilation and curettage. Once a diagnosis has been made, treatment options include medical therapy with methotrexate and surgery, which can often be performed via the laparoscope. Fertility rates after therapy are similar for both medically and surgically treated patients.
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