Modulation of antioxidant enzyme activities by sexual steroid hormones

Taking into consideration the biological importance of interaction between antioxidant defense (AD) enzymes and sexual steroid hormones it was deemed important to compare our recent achievements in the field with the state of current knowledge. The main goal of the present review was to investigate the changes of AD enzyme activities: superoxide dismutases, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase in the brain of female and male rats depending on progesterone and estradiol. These ovarian steroids produce their effects by acting on numerous target tissues and organs, such as the reproductive organs, bone tissue and cartilage, peripheral blood vessels and the central nervous system (CNS). We have chosen it as a new parameter that might represent an important indicator of the changes within the CNS, bearing in mind the biological importance of the enzymes of the AD system. Our experimental results indicate that the AD enzyme activities in the brain tissue of female and male rats show a certain dependence on the concentration of progesterone and estradiol. The present review suggests that the modulation of the oxidative and antioxidative capacity by sexual steroid hormones is mediated through antioxidant metabolizing enzymes.     

Compositional changes in the rat femur following ovariectomy

Ovariectomy has been shown to produce osteoporosis in the femur of the rat. 11-month-old Sprague-Dawley rats were either ovariectomized or given a sham operation. The loss of calcium in the femur of the rats was compared with two indices of osteoporosis, the ponderal index and the femur score. The calcium content was more closely associated with the femur score (r = 0.5, p = 0.0064) than with the ponderal index (r = -0.367, p = 0.05). An accelerated rate of fat deposition in the ovariectomized rat femur reduced the femur weight loss, which resulted in a barely significant association of calcium content with the ponderal index.     

Hormonal modulation of extinction responses induced by sexual steroid hormones in rats

A functional interrelation between the nervous and endocrine systems has been established. However, few studies have dealt with the effects of sexual steroids on learning and memory. The aim of this work was to determine whether sexual steroid hormones could modulate the extinction response of a passive avoidance conditioning in rats. Male Wistar rats, randomly assigned to five groups, two controls and three experimental groups, were submitted to a one-trial passive avoidance conditioning and tested for their retention 24 hr after and during 10 weeks. One control group received no treatment at all, the other received vegetable oil, and the three experimental received 20 mg of testosterone enanthate, 0.8 mg estradiol valerate, or 4 mg nandrolone decanoate, respectively. All substances were applied in a 0.3 ml volume, 24 hours before training and before testing for retention each week during 10 weeks. Results indicate that the extinction process is modulated by these hormones, since testosterone and estradiol facilitate extinction, whereas the anabolic androgen produced a resistance to the extinction process.     

Modulation of short term and long term memory by steroid sexual hormones

Many studies have evidenced a functional interrelation between the nervous and endocrine systems in the modulation of mnemonic processes, and others have established the role played by certain hormones in these processes; however, few studies have dealt with the effects of sexual steroids on learning and memory. The aim of this work was to determine whether shortterm and long-term memory is subject to hormonal modulation. Male Wistar rats, randomly assigned to 13 groups, 1 control and 12 experimental groups, were trained on a one-trial passive avoidance conditioning. The control group received saline solution, and each of the 12 experimental groups received a treatment consisted in one of following pharmacological doses of: 5, 10, 20, 30 mg of testosterone enanthate, 0.2, 0.4, 0.8, 1.2 mg estradiol valeriate, or 1, 2, 4, 6 mg norandrostenolone decanoate, respectively. All substances were applied 45 min before the training session. Retention of the learned response was tested 10 min (short-term memory) and 24 h (longterm memory) after the training session. Results indicate that under these experimental conditions the short-term memory is facilitated with testosterone enanthate at doses of 20 and 30 mg, the estradiol valeriate at doses of 0.4 mg and the nor-androstenolone decanoate at doses of 4 mg, whereas the long-term memory is facilitated with testosterone enanthate at doses of 30 mg, estradiol valeriate at doses of 1.2 mg and the nor-androstenolone decanoate at doses of 4 mg. The other studied doses were no effective.     

Effects of acute unilateral ovariectomy to pre-pubertal rats on steroid hormones secretion and compensatory ovarian responses

In the present study we analyzed the existence of asymmetry in the secretion of steroid hormones in pre-pubertal female rats treated with unilateral ovariectomy (ULO) or unilateral perforation of the abdominal wall (sham-surgery). Treated rats were sacrificed at different times after surgery. Since sham-surgery had an apparent effect on the age of first vaginal estrous (FVE) and serum levels hormone, the results of the sham surgery groups were used to assess the effects of their respective surgery treatment groups. On the day of FVE, compensatory ovulation (CO) and compensatory ovarian hypertrophy (COH) were similar in animals with ULO, regardless of the ovary remaining in situ. In ULO treated animals, progesterone (P4) levels were higher than in animals with sham-surgery one hour after treatment but lower in rats sacrificed at FEV. Left-ULO resulted in lower testosterone (T) concentration 48 and 72 hours after surgery. In rats with Right-ULO lower T concentrations were observed in rats sacrificed one or 72 hours after surgery, and at FVE. ULO (left or right) resulted in lower estradiol (E2) concentrations one or 72 hours after treatment. In rats with Left-ULO, E2 levels were higher 48 hours after surgery and at FVE. Left-ULO resulted in higher levels of follicle stimulating hormone (FSH) five hours after surgery and at FVE. FSH levels were higher in rats with Right-ULO sacrificed on FVE. The present results suggest that in the pre-pubertal rat both ovaries have similar capacities to secrete P4, and that the right ovary has a higher capacity to secrete E2. Taken together, the present results support the idea that the effects of ULO result from the decrease in glandular tissue and changes in the neural information arising from the ovary.     

Effects of sexual steroid hormones on the functionality of murine peritoneal macrophages.

In the present work, we studied the possible effect of steroid hormones, estradiol, progesterone, and 5 alpha-dihydrotestosterone, on different phenotypic and functional characteristics of peritoneal adherent mononuclear cells. We used female and male mice of Balb/c strain, normal, gonadectomized, and gonadectomized with hormonal replacement. We found that gonadectomy in both sexes produced a significant decrease in the functionality of membrane receptors for the complement and in phagocytic activity of Candida albicans-anti-C albicans system. In addition, the percentages of cells that reduced nitroblue tetrazolium were diminished in castrated animals. Ovariectomized females injected with estradiol presented normal levels of phagocytic and metabolic capacities, but the expression of membrane receptors for complement remained decreased. In contrast, progesterone treatment of ovariectomized animals had the opposite effect. Simultaneous treatment with estradiol plus progesterone gave results similar to those observed with estradiol only. Dihydrotestosterone per se did not affect any of the parameters measured in the conditions used here. These results suggest that female steroids affect macrophage functionality, probably by regulating surface receptors that are involved in phagocytic activity.     

Development of the renal sexual segment in immature snakes: effect of sex steroid hormones

The renal sexual segment (RSS) of immature Northern and Diamondback Water Snakes and Red-Sided Garter Snakes exhibited varying responses to testosterone or 17beta-estradiol. In both male and female water snakes, kidney mass was not a reliable indicator of hormone treatment, whereas tubule diameter, epithelial height and number of sexual granules responded to hormone treatment. In male water snakes, either hormone initiated granule development by day 16; by day 23, only testosterone increased granule density. Female water snakes receiving either hormone exhibited a small number of granules by day 16; by day 23, granules increased only in Diamondback Water Snakes receiving testosterone. Hormones did not initiate RSS hypertrophy in female Red-Sided Garter Snakes. Tubule diameter and epithelial height of testosterone-treated males exhibited significant hypertrophy, while 17beta-estradiol initiated significant increases in tubule diameter. Garter snakes initiated sexual granule development in response to hormone treatment with males exhibiting a greater response than females and testosterone stimulating a greater response than 17beta-estradiol. Sex steroids appear to mimic sexual maturity in immature snakes initiating RSS development. Whereas the RSS of adult males respond to testosterone, our data suggest specific changes in the RSS of females during maturation effectively negates the effect of 17beta-estradiol evident in immature female RSS.     

Gonadotropin and steroid hormones stimulate proliferation of the rat ovarian surface epithelium

The ovarian surface epithelium (OSE) is a single layer of flattened or cuboidal cells covering the ovary. Ninety percent of all human ovarian malignancies arise from this layer of cells. Incessant ovulation, hyperovulation induced by infertility treatment, and hormone replacement therapy have been suggested as risk factors for ovarian cancer. In this study, two groups of rats, with and without surgically induced injury to the ovary, were treated with 17beta-estradiol, pregnant mare's serum gonadotropin (PMSG), human chorionic gonadotropin (hCG), or the combination PMSG/hCG, and the proliferative response of the OSE cells was measured using bromodeoxyuridne (BrdU) and (3)H-thymidine. All hormones, alone or in combination with ovarian surgery, were found to increase significantly the rate of proliferation of the rat OSE. These data demonstrate that hormones associated with infertility treatments and hormone replacement therapy, as well as injury- or ovulation-induced rupture of the ovarian surface, stimulate the rat OSE, and hence could have a role in the development of ovarian cancer via proliferation-associated mutagenesis, or alternatively, by promoting the rapid selection of OSE cells with accumulated mutations.     

Quantitative variations in the number and size of peritoneal mastocytes in the female rat during the normal sexual cycle, following ovariectomy and administration of estrogens

Female rat peritoneal mast cells were found more numerous and of more reduced sizes in metestrus and diestrus than in proestrus and especially estrus where a partial degranulation took place. Ovariectomy caused an important decrease in the number and size of mast cells. A regular treatment of spayed animals by 17 beta estradiol partly inhibited these effects.     

Time-studies of the changes in the sex-dependent activities of enzymes of hepatic steroid metabolism in the rat following gonadectomy.

The activities of cytoplasmic 3 alpha- and 17 beta-hydroxysteroid dehydrogenase, microsomal 3 alpha- and 3 beta-hydroxysteroid dehydrogenase and microsomal 5 alpha-reductase of rat liver were determined at different time points after gonadectomy on day 75 of life. Following testectomy the activities in male rats assume female values. However this change is relatively slow, 10--14 days being necessary for significant trends in individual activities to develop, and 40--60 days before the final level of activity is reached. The changes in enzyme activities after ovariectomy are only slight. The change in microsomal 5 alpha-reductase activity following gonadectomy of male rats is biphasic, the activity increasing initially to the normal female level before falling to the intermediate "neonatally androgen-imprinted" level. The reaction of 17 beta-hydroxysteroid dehydrogenase activity to testectomy and ovariectomy indicates that in the course of several years, during which we have investigated the behaviour of this enzyme in Chbb/THOM rats, the regulation of its activity has changed from one of oestrogen dependency to one of androgen dependency.     

Effects of ovariectomy and steroid replacement on GABAA receptor binding in female rat brain.

The specific binding of tritiated muscimol to gamma-aminobutyric acid (GABA) receptor sites was studied in distinct brain areas of female rats during different endocrine states. In diestrous rats with intact ovaries the highest receptor densities were found in the cortex (10.24 pmol/mg protein) and the lowest concentrations in the mediobasal hypothalamus (3.29 pmol/mg protein). Four weeks after removal of the ovaries, the number of binding sites was enhanced up to 2.4-fold in all brain areas investigated: the preoptic brain area, mediobasal hypothalamus, corticomedial amygdala, and cerebral cortex. The affinity of the binding sites remained unchanged. Substitution of estradiol and progesterone reduced the number of binding sites to values seen before ovariectomy. The induction of an afternoon surge of LH by estradiol that could be blocked by enhancing the GABAergic tone was accompanied by a distinct reduction in Bmax in the preoptic area in the morning. These results give evidence that ovarian hormones modulate GABAergic neurotransmission by regulation of GABAA receptor synthesis or degradation.