Influence of sex steroids on development of cultured fetal rat metatarsal bones

The effects of 17 beta-estradiol (E), dihydrotestosterone (D, a non aromatisable androgen), and progesterone (P) on osteogenesis were studied on fetal rat cartilaginous anlagues cultivated in vitro. The three medial metatarsal rudiments were harvested at day 19 of gestation and grown in 1% BSA MEM medium (MO 643, Sigma) without serum nor antibiotics. After a 18h preincubation period, hormones were added for 8 days. Paired controls were incubated in the same volume of medium. The length, the metacarpal thickness and the size of the mineralized zone were measured every day, using a calibrated eyepiece (magnification X 40). DNA and protein synthesis, cartilage metabolism and mineralization were evaluated by monitoring the incorporation of 3H-Thymidine, 3H-Proline, 35S and 45Ca into anlagues for the last three hours of incubation, respectively. The dose/response effect of each steroid was studied at the concentrations of 10(-4) M, 10(-6) M, 10(-7) M and 10(-9) M. No difference was observed between male and female fetuses. A significant positive effect on total length (% of length measured at harvesting day) was observed with the 10(-7) M dose of E (163% +/- 2 vs 148% +/- 4 in controls) or D (158% +/- 3). Endochondral growth was not modified by P treatment. The effect of the three steroids (given at a dose of 10(-7) M) alone or as combinations (E, D, P, EP, ED, PD, EPD) confirmed the positive effect of E on endochondral growth and, to a lesser extend, of D and the association ED. Nevertheless, D had a better effect than E on endomembranous growth. On the contrary, P did not affect growth neither administrated alone nor in combination with E or D, while a positive effect of P on mineralization was demonstrated. The treatment associating the three steroids slowed down all the parameters concerning growth but strongly stimulated calcification.     

Role of female sex steroids in regulating cholesteryl ester transfer protein in transgenic mice

The role of sex steroids in the regulation of cholesteryl ester transfer protein (CETP) was examined in the following groups of female transgenic mice carrying the human CETP gene: (1) normal, (2) ovariectomized, (3) ovariectomized and treated with estrogen; (4) ovariectomized and treated with progesterone; (5) ovariectomized and treated with both hormones, and (6) ovariectomized and treated with tamoxifen. CETP activity was measured in the plasma, and in the particulate and the soluble fractions of liver, muscle, and adipose tissue. Human CETP specific activity was determined by taking the difference of cholesterol ester transfer in the presence and absence of an antibody (TP2) against human CETP Ovariectomy reduced hormone levels, but did not completely abolish them from the circulation. Plasma CETP activity was significantly reduced in the tamoxifen group. There were significant reductions in CETP in liver homogenate and the soluble fraction, as well as in the particulate fraction of adipose with ovariectomy. Hormone replacement did not restore CETP activity in either the plasma or the tissues. Tamoxifin treatment resulted in a decrease in CETP activity in both fractions of liver, but had no effect on adipose. In the soluble fraction of adipose tissue and both fractions of muscle, only trace CETP activity was detected. We conclude that (1) minimal amounts of sex steroid hormones may be sufficient to affect CETP expression; (2) the effects of sex steroid hormones vary among tissues; and (3) in addition to the sex steroids, factor(s) from the ovary are needed for the full expression of CETP in this animal model.     

Urea, glucose and alanine kinetics in man: effects of glucose infusion

1. The simultaneous effects of an intravenous glucose infusion on plasma urea, glucose and alanine kinetics were investigated in normal post-absorptive man. 2. The primed constant intravenous infusion of compounds labelled with stable isotopes, [15N2]urea, [6-2H]glucose and [3-13C]alanine, was used. 3. The rate of appearance of glucose and urea in the plasma was rapidly reduced by the 17.7 mumol min-1 kg-1 glucose infusion. 4. In contrast, during the glucose infusion there was an increased rate of appearance of alanine in the plasma, and an increased percentage of glucose carbon atoms derived from alanine. 5. Reduced production of glucose and urea during the glucose infusion was not due to decreased gluconeogenesis from alanine.     

Effect of sex hormones on oxalate-synthesizing enzymes in male and female rat livers

PURPOSE: We studied the effect of changes in sex hormones on oxalate metabolism in rats. MATERIALS AND METHODS: Adult male and female rats were administered a precursor of oxalate, and the relationship between dose and urinary oxalate was examined. Levels of sex hormones were varied in rats and glycolate oxidase (GO) and serine pyruvate aminotransferase (SPT) activities were measured under the conditions of being fed tap water or loading with 0.5% ethylene glycol. In addition, urinary oxalate excretion was evaluated. RESULTS: Ethylene glycol and glycolate increased urinary oxalate concentration in male rats dose-dependently but less in female rats. There was almost no change during glycine loading in either male or female rats. GO activity was significantly lower in intact female and gonadectomized male rats. SPT activity was slightly higher in the female than in the male controls. There were no differences in urinary oxalate excretions between male and female rats. During ethylene glycol loading, GO and SPT activities were similar to those with tap water intake. However, urinary oxalate excretion increased to two times the control value in male rats but only slightly increased in female rats. CONCLUSIONS: Sex-related differences exist in the metabolic conversion of glycolate to oxalate in rats, and GO activity is promoted by testosterone. Although difference in GO activity has no physiological effect on oxalate synthesis, GO activity affects urinary oxalate excretion during ethylene glycol loading. We could also conclude that estrogen decreases GO activity in male rats from our results.     

Progesterone receptor isoforms are differentially regulated by sex steroids in the rat forebrain

We studied the effects of estradiol (E2) and progesterone (P4) on expression of genes coding for PR isoforms in the forebrain of ovariectomized rats by RT-PCR analysis. In the hypothalamus the expression of both PR isoforms was induced by E2 and down-regulated by P4. In the preoptic area these changes were only observed in the PR-B isoform. In contrast, in the hippocampus PR induction by E2 was only observed for PR-A. In this region P4 did not modify the expression of any PR isoform. These results indicate that PR isoforms expression is differentially regulated by sex steroid hormones in distinct forebrain regions and suggest that the tissue-specific regulation of either PR-A or PR-B may be involved in the physiological actions of P4 upon the rat brain.     

Peripheral effects of sex steroids: implications for patient management

Sex steroids--estrogens, progesterone, and testosterone and other androgens--have effects on the anatomy and physiology of many nonreproductive organ systems. These changes can influence the sex ratio of certain diseases. They also affect the "normal range" for certain parameters, and data from men often do not apply to normal female physiology. Sex steroids also affect the response to certain toxins, pharmacologic agents, and other therapies. Replacement sex steroid therapy and oral contraceptives may affect these processes differently than natural hormones do. The normal monthly changes of female hormones can also affect the severity of many conditions and may change the response to therapy in certain conditions, such as asthma or control of diabetes. This paper reviews the data on the effects of sex hormones on normal and pathologic human physiology and examines the therapeutic implications of these findings.     

Intercellular communication within the rat anterior pituitary gland: VI. Development of gap junctions between folliculo-stellate cells under the influence of ovariectomy and sex steroids in the female rat

BACKGROUND: Farquhar (1957) initially described the folliculo-stellate cells in the rat anterior pituitary gland and found them to be located in groups around follicles throughout the anterior lobe. Soji and his co-workers have published a series of reports concerning cell-to-cell communication in the male rat hypophysis involving folliculo-stellate cells as mediated through a gap junctional network and recorded a reduction in junctional number following castration that was reversed by the administration of testosterone (Soji and Herbert, 1990, Anat. Rec., 226:342-346; Soji et al., 1990, Anat. Rec., 226:337-341). METHODS: Animals were ovariectomized at 10 days of age and separated into three groups: (1) intact control, (2) ovariectomized controls, (3) ovariectomized and given either estradiol, testosterone, or progesterone. On days 10, 20, 30, 40, and 45, the pituitary gland from animals in each group was removed and processed for ultrastructural examination. RESULTS: Gap junctions in the intact control female rats initially appeared between adjacent folliculo-stellate cells on day 20. Their numbers linearly increased until the animals reached the age of 45 days. In contrast, there was a suppression in the number of gap junctions present in the ovariectomized groups and a marked enhancement of the junctions in each of the three steroid-treated groups. CONCLUSIONS: These findings support the observations made in the male rat in which it was found that the development of gap junctions in the anterior pituitary gland of the rat is dependent in part on the presence of sex steroid hormones.     

The effects of sex steroids on spatial performance: A review and an experimental clinical investigation.

Males typically surpass females in spatial performance, an outcome that may be linked to testosterone and estrogen. The authors (a) review physiological mechanisms, developmental periods, and past empirical work relevant to sex steroids' effects on human spatial performance and (b) report an experimental study of the role of actively circulating sex steroids in 55 adolescents being treated for delayed puberty (mean age 13.70 yrs). Sex steroids (stimulating early, middle, and late puberty) and placebos were given alternately over 21 months and spatial tests were given every 3 months. Spatial performance showed traditional sex differences but did not vary with levels of actively circulating sex steroids. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A PET study of Turner's syndrome: effects of sex steroids and the X chromosome on brain

Women with Turner's syndrome (TS) allow us to study the neurobiological associates of cognitive and behavioral abnormalities because they lack one/part of one X chromosome, and endogenous estrogen. We studied 13 healthy controls (mean age +/- SD, 28 +/- 6 years) and 16 TS subjects (mean age +/- SD, 26 +/- 6 years). We measured cognitive abilities using neuropsychological tests, and cerebral metabolic rates for glucose with positron emission tomography. Compared to controls, TS subjects had significant absolute hypermetabolism in most brain areas; however, normalized metabolism was significantly lower in TS subjects than controls in the insula and association neocortices bilaterally, and there were significant differences in functional metabolic associations of brain region pairs originating in occipital cortex bilaterally, and within the right hemisphere. There were significant correlations between right-left cognitive and metabolic asymmetries in the TS group. Also, within TS a preliminary analysis demonstrated "X chromosome dosage" effects in language ability and left temporal metabolism, asymmetry of right-left test scores, and parietal metabolism. We hypothesize that within TS: i) generalized brain hypermetabolism reflects global abnormalities in neuron packing; ii) neuronal abnormalities occur in association neocortex that differ in nature or extent from whole brain and are associated with significant differences in normalized metabolism; iii) cognitive deficits are related to brain metabolic abnormalities; and iv) social-behavioral problems may be related to abnormalities of brain metabolism. Moreover, in human brain the X chromosome involved in development of the association neocortices.     

Age and sex dependence of the effects of an aqueous extract of Physalis alkekengi fruits on rat hepatic glucose 6-P dehydrogenase activity

Intraperitoneal injections of an aqueous extract of winter cherry fruits (Physalis alkekengi) to new-born, weanling and adult female rats and to weanling and adult male rats had no effect on body weight, liver weight and liver cytosol protein content. The specific activities of hepatic glucose 6-P dehydrogenase (an estrogen induced protein) in rats of different age and sex groups in terms of mU/mg protein were: treated new-born females, 15.9 +/- 0.5; control, 29.1 +/- 0.6; treated weanling females, 14.9 +/- 0.3; control, 24.8 +/- 0.7; treated adult females, 25.7 +/- 0.5; control, 26.1 +/- 0.5; treated weanling males, 7.9 +/- 0.2; control, 7.9 +/- 0.1; treated adult males, 9.6 +/- 0.4; and control, 9.7 +/- 0.3. Treatment of new-born and weanling female rats with the extract resulted in 40-45% reduction in hepatic G6PD activity. However, treatment of adult females, and weanling and adult males produced no significant change in the activity of this enzyme. The data are discussed both in terms of the increase in the capacity of rodent liver to metabolize steroidal compounds with age and the presence of low levels of circulating estradiol necessary for enzyme induction in male rats.     

Seasonal variation of neuropeptide Y actions on growth hormone and gonadotropin-II secretion in the goldfish: effects of sex steroids

Tumor lysis syndrome is a critical illness characterized by massive tumor cell death leading to severe hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and acute renal failure in patients with rapidly growing cancers (especially Burkitt's lymphomas with extensive abdominal bulk). It may be preventable with allopurinol therapy combined with aggressive intravenous fluid therapy aimed at establishing an ongoing alkaline diuresis. In most cases renal failure is completely reversible; however, fatal hyperkalemia and volume overload may develop. Therefore, aggressive management with hemodialysis often is necessary to maintain life support while tumor burden is controlled with cytoreductive therapy. Early recognition and management by a team approach in the intensive care unit where careful monitoring is available serves to forestall severe renal failure, thereby improving short-term prognosis in susceptible patients.     

The roles on intraluminal oxygen and glucose in the protection of the rat intestinal mucosa from the effects of ischaemia

Rat ileal loops were subjected to 15 minutes ischaemia by clamping both mesenteric and collateral vessels, after which the functional capacity of their mucosae was assessed according to their ability to accumulate phenylalanine "in vitro". Groups of intestines were rinsed before being subjected to ischaemia. Independent and additive protective effects were observed when the rinsing buffer was oxygenated and/or when it contained glucose. Indeed, an oxygenated, glucose-containing buffer afforded full protection to the mucosa, whereas a nitrogenated, glucose-free buffer had no action.     

Effects of sex steroids on sensory and motor spinal mechanisms

The male copulatory pattern uses muscles in the penis for erection and penile insertion, the lower trunk for pelvic thrusting, and the sex accessory organs for seminal emission. Organization of the nuclei controlling penile muscles is achieved through cell growth, dendritic arborization, and synaptogenesis, actions dependent on androgen but not estrogen. Testosterone (T) and dihydrotestosterone (DHT) but not estradiol (E2), stimulate pelvic thrusting vigor by synchronizing discharge of motoneurons innervating pelvic muscles. Pelvic thrusting rhythmicity, regulated by spinal interneurons, is produced in female rabbits by E2 or T but not by DHT. Reflex contraction of the seminal vesicles, due to penile insertion, is facilitated by androgen presumably by its effect on preganglionic neurons of the hypogastric nerve, located in the dorsal commissural nucleus.     

Training effects on maternal and fetal glucose uptake following acute exercise in the rat

The purpose of the present study was to determine the effects of chronic maternal exercise on glucose uptake in maternal tissues after one bout of treadmill running during late gestation in the rat and to determine the effects on glucose accumulation in the fetus and placenta. Trained pregnant animals (PR) ran at 30 m.min-1, on a 10 degrees incline for 1 h on day 20 of gestation with a similarly treated trained nonpregnant group (NPR). Immediately after the run the animals were infused with a bolus of 1 g.kg-1 body wt as a 50% dextrose solution mixed with 2-deoxy-D-[1-3H] glucose through a carotid catheter. Sedentary pregnant (P) and nonpregnant animals (C) were also infused with the solution after no food and water for the same time frame. After 60 min, tissues were analyzed for radioactivity. Radioactive tracer was augmented in the red gastrocnemius and soleus of the PR group and the soleus of P rats. However, tracer accumulation in the fetus and placenta of the trained animals was not different than P animals. These results indicate that acute exercise in trained animals increased glucose uptake in maternal skeletal muscles without compromising conceptus glucose accumulation.     

Local transport kinetics of glucose during acute and chronic nicotine infusion in rat brains

Acute and chronic infusion of nicotine is known to result in a distinct increase in local cerebral glucose utilization (LCGU) in several brain structures. The present study addresses the question whether this increase in LCGU is paralleled by a local change in glucose transport in rat brain. Nicotine was infused either acutely for 3 hours or chronically by osmotic minipumps for one week. Local rate constants for glucose transport were measured in brain cryosections using the 3-O-[14C]methylglucose method. Local rate constants K1 and k2 were lower in part of the brain structures during acute (-10% to -20%) and in nearly all structures during chronic (-39% to -41%) nicotine. The finding of a decreased glucose transport during chronic nicotine was confirmed by additional experiments of 3-O-[14C]methylglucose transfer in an epithelial cell culture. It is concluded that acute and chronic nicotine infusion results in decreased glucose transport although LCGU is either unchanged or increased.     

The influence of sex hormones on obesity across the female life span

Women have a higher prevalence of obesity than men in most developed countries. Obesity affects many aspects of women's health by increasing risk for heart disease, diabetes, breast cancer, and infertility. One reason for the gender difference in obesity may be that fluctuations in reproductive hormone concentrations throughout women's lives uniquely predispose them to excess weight gain. Studies in experimental animals and women have shown that hormonal changes across the menstrual cycle affect calorie and macronutrient intake and alter 24-hour energy expenditure. Pregnancy is a significant factor in the development of obesity for many women. Various factors are associated with excess weight retention following pregnancy, including weight gain during pregnancy, ethnicity, dietary patterns, and interval between pregnancies. There is a need to tailor recommendations for energy intake during pregnancy to individual women, and recent evidence also suggests that the timing of weight gain during pregnancy is a critical factor. Menopause is also a high-risk time for weight gain in women. Although the average woman gains 2-5 pounds during menopausal transition, some women are at risk for greater weight gains. There is also a hormonally driven shift in body fat distribution from peripheral to abdominal at menopause, which may increase health risks in older women. Hormone therapies have varying impacts on body weight and fat distribution. In summary, hormonal fluctuations across the female life span may explain the increased risk for obesity in women. Awareness of these factors allows development of targets for prevention and early intervention.     

Behavioral effects of alpha-MSH and MCH after central administration in the female rat

The behavioral effects of alpha-MSH, MCH, and alpha-MSH + MCH were investigated in the ventromedial nucleus (VMN) and medial preoptic area (MPOA) (bilateral, 100 ng in 0.5 microliter). Infusion of alpha-MSH into the VMN increased aggressive behavior; in the MPOA it reduced exploration and increased anxiety. In both areas it stimulated sexual behavior. MCH also stimulated sexual behavior in the MPOA and VMN and had an anxiogenic effect in the MPOA. The effect of alpha-MSH on aggression and exploration was antagonized by MCH. When given together, the two peptides were mutually antagonistic on anxiety. This study indicates that MCH has central nervous system effects and may be a partial alpha-MSH agonist.     

Influence of sex steroids on the secretory function of the epididymis in castrated rats

Secretory response of the epididymis to exogenously administered testosterone, estrogen and progesterone was investigated using the levels of sialic acid and glycerylphosphorylcholine as indices. Testosterone was found to be most potent in stimulating the (GPC) secretory function of the organ. An enigmatic finding of the present study was that while estrogen showed the ability to stimulate both sialic acid and GPC levels, progesterone exerted its influence only on sialic acid. Studies on the accessory genital organs (weight of seminal vesicles and ventral prostate and fructose level of coagulating gland) also revealed a stimulatory effect of the steroids.     

Prevention of bone loss following oophorectomy in premenopausal women: a retrospective assessment of the effects of oophorectomy and a prospective controlled trial of the effects of mestranol therapy

Prospective studies of bone mass in women following oophorectomy for benign conditions were done by the double-blind technique. Skeletal response to treatment was measured by photon absorption densitometry. Untreated patients were found to lose bone mass rapidly during the first two years after oophorectomy. When estrogen replacement was started within two months of oophorectomy, it was found to be effective in preventing subsequent bone tissue loss. Three years following oophorectomy, untreated women who had already lost bone tissue, and who were then started on estrogen replacement, showed a highly significant increase in their bone mass. The women in whom this treatment was delayed for six years did not respond. No untoward effects were noted in these women, perhaps, in part, because they had undergone hysterectomy. Long-term effects of this treatment are now being evaluated.     

The effect of stevioside on glucose metabolism in rat

This study was conducted to determine the effect of stevioside (SVS) on glucose metabolism. The experiments were performed in male Wistar rats treated with SVS either by intravenous infusion or feeding. SVS infusion (150 mg/mL) was carried out in doses of 0.67, 1.00, and 1.33 mL.kg-1 body weight.h-1. The plasma glucose level significantly increased both during and after SVS infusion, whereas it was not affected by SVS feeding (13.3 mL.kg-1 body weight). The glucose turnover rate (GTR) of [14C(U)]glucose and [3(-3)H]glucose was not significantly different between control and SVS infusion animals. Percent glucose carbon recycling and glucose clearance were reduced from 28.7 +/- 1.3 to 23.0 +/- 1.6% (p < 0.05) and from 6.46 +/- 0.34 to 4.99 +/- 0.20 mL.min-1.kg-1 body weight (p < 0.01), respectively. The plasma insulin level did not change, whereas the plasma glucose level significantly increased from 120.3 +/- 5.9 to 176.8 +/- 10.8 mg% (p < 0.01) during SVS infusion. Animals pretreated with angiotensin II and arginine vasopressin showed no significant effect, while animals pretreated with prazosin had an attenuated hyperglycemic effect of SVS infusion. Pretreatment with indomethacin or N omega-nitro-L-arginine methyl ester (L-NAME) alleviated the plasma glucose level during the second period of SVS infusion. Pretreatment with the combination infusion of indomethacin and L-NAME reduced the plasma glucose level from 117.0 +/- 1.8 to 109.0 +/- 1.7 mg% (p < 0.001), and normalized the plasma glucose level in the second period of SVS infusion. Insulin infusion inhibited the hyperglycemic effect of SVS infusion. The present results show that the elevation of the plasma glucose level during SVS infusion is not due to the reduction of the insulin level. It is probably the effect of SVS on glucose transport across the cell. Insulin response to a high plasma glucose level is suppressed during SVS infusion. Several interactions among norepinephrine, prostaglandin, and nitric oxide are involved in modulating the hyperglycemia during SVS infusion.