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.     

Prostaglandin in teh uterus: Modulation by steroid hormones

Phospholipase A₂ (PLA₂), one of the enzymes considered to be rate-limiting in generating free arachidonic acid for prostaglandin (PG) synthesis, endogenous concentrations and $\text{in vitro}$ production of PGs in the rat uterus were studied under various experimental conditions. Uterine PLA₂ activity showed a 167-fold increase in ovariectomized rats bearing estradiol-17 β (E₂)-implants as compared to those treated with vehicle only. On the other hand, dexamenthasone treatment reduced the E₂-stimulable PLA₂ activity by about 24-fold. The uterine PLA₂ activity in the ovariectomized rat uterus was low and not altered by instillation of progesterone (P₄) implants or by administration of dexamethasiome. On the contrary, simultaneously placement of E₂- and P₄-implants prevented significantly the rise in PLA₂ activity as observed under upposed E₂ exposure. Dexamethasome treatment further reduced the activity. The endogenous concentration of uterine PGF was several fold higher in the E₂-implanted ovariectomized rats as compared to those without the E₂-implants or carrying only P₄-implants. The simulataneous treatment of the E₂-implanted rats with P₄ and/or dexamethasone reduced the uterine PGF concentrations considerably. The uterine PGF concentration was always lower in the ovariectomized rats under any condition if they were not treated with E₂. Uterine PGE-A concentration did not change significantly between the ovariectomized rats and the ovariectimized rats carrying E₂-implants. The treatment with P₄ and/or dexamethasome, however, tended to decrease the PGE-A concentration. The production of PGF by the uterine homogenate increased by several fold in ovariectomized rats implanted with E₂-silastic capsules as compared to those without the e₂ implants. The treatments of the E₂-implanted rats with P₄ or dexamethasome did not alter this production. However, simultaneous exposure of E₂-implanted rats to P₄ and dexamethasone lowered the production rate of PGF in the uterus. The treatment of the ovariectomized rats with dexanethasome or P₄ tended to elevate the uterine PGF production. The uterine PGE-A production followed more or less the same pattern. The analysis of our present data suggest that although a relationship exists between uterine PLA₂ activity and PGD concentration, the role of PG synthetase could also be important in regulating PGF synthesis. Our study with dexamethasome, which showed inhibition of uterine PLA₂ activity and decline in endogenous but not $\text{in vitro}$ production of PGs, indicate that cellular integrity is essential for PLA₂ of function as a rate-limiting step in PG synthesis. The present findings also imply that alteration in PLA₂ or PG synthesis has little influence on PGE formation and the latter is not sensitive, to any great extent, to steroid hormonal changes. We considere that fluctuation in PGF/PGE ratio is mainly due to fluctuation in PGF level under various conditions.     

Newly proliferated cells in the adult male amygdala are affected by gonadal steroid hormones

Gonadal steroid hormones play an important role in the proliferation, survival, and activation of neurons. The present study was performed to examine the effects of testosterone and its metabolites on newly proliferated cells in the amygdala of adult male meadow voles (Microtus pennsylvanicus). Treatment with testosterone propionate (TP) in castrated males resulted in plasma testosterone levels similar to males following mating. TP-treated males displayed a significant increase in the density of cells labeled with a cell proliferation marker (BrdU) in the amygdala. Treatment with estradiol benzoate (EB) exerted a similar effect as TP on the density of BrdU-labeled cells, whereas 5alpha-dihydrotestosterone (DHT) was ineffective. A larger proportion (approximately 44%) of the BrdU-labeled cells in the amygdala displayed a neuronal phenotype, and a lesser percentage (approximately 35%) displayed a glial progenitor phenotype; however, treatment effects were not found in either population of cells. Hormonal effects appeared to be site-specific as no group differences were found in the dentate gyrus of the hippocampus or ventromedial hypothalamus. Finally, a time course study indicated that BrdU-labeled cells in the amygdala are present as early as 30 min following an acute injection of BrdU. Together, these data suggest that gonadal steroid hormones influence the number of newly proliferated cells in the amygdala, most likely by acting through an estrogenic mechanism, and these effects may be exerted on locally proliferating progenitors within the amygdala.     

Long-term cerebral cortex protection and behavioral stabilization by gonadal steroid hormones after transient focal hypoxia

Sex steroids are neuroprotective following traumatic brain injury or during neurodegenerative processes. In a recent short-term study, we have shown that 17β-estradiol (E) and progesterone (P) applied directly after ischemia reduced the infarct volume by more than 70%. This protection might primarily result from the anti-inflammatory effects of steroids. Here, we focus on the long-term neuroprotection by both steroids with respect to the infarct volume, functional recovery, and vessel density in the penumbra. The application of E/P during the first 48h after stroke (transient middle cerebral artery occlusion, tMCAO) revealed neuroprotection after two weeks. The infarct area was reduced by 70% and motor activity was preserved compared to placebo-treated animals. Blood vessel density in the penumbra using immunohistochemistry for von Willebrand factor showed increased vessel density after tMCAO which was not affected by hormones. Expression of vascular endothelial growth factor (VEGF) and its receptor (R1) was increased at 24h after tMCAO and up-regulated by E/P but not changed 14 days after stroke. These findings suggest that the neuroprotective potency of both steroids is sustained and persists for at least two weeks. Besides anti-inflammatory and anti-apoptotic actions, angiogenesis in the damaged area appears to be initially affected early after ischemia and is manifested up to two weeks. This article is part of a Special Issue entitled 'Neurosteroids'.     

Phospholipase A2 activity in the rat uterus: Modulation by steroid hormones

Phospholipase A2 (PLA2), an enzyme which provides free arachidonic acid for the synthesis of prostaglandins (PG), has been studied in the rat uterus under various experimental conditions. Uterine PLA2 activity increased 14 fold in hypophysectomized rats implanted with Silastic capsules containing estradiol-17β as compared to those treated with oil vehicle. Dexamethasone treatment reduced the PLA2 activity induced by estrogen by 78%. Hypophysectomized animals treated with progesterone (2mg/day) for 5 days had low levels of uterine PLA2 activity but a single injection of estradiol (10ug/rat) given 24 h after the last injection of progesterone increased activity 5 fold within 12 h. Administration of the protein synthesis inhibitor cycloheximide in the rats treated with progesterone, before and after injection of estradiol, prevented the stimulating action of the estrogen on PLA2 activity. If the estrogen was given at the time of the last injection of progesterone, PLA2 activity did not increase until 24 h later and the level was much less than when progesterone was absent. The results are consistent with the view that estrogen stimulates uterine prostaglandin production because of its effect upon PLA2; this effect can be greatly reduced by a glucocorticoid. Progesterone may modulate the PLA2 stimulating effect of estrogen in order to direct the production of specific PGs by regulating the amount of arachidonic acid available for PG synthetase.     

Gastrointestinal hormones regulating appetite

The role of gastrointestinal hormones in the regulation of appetite is reviewed. The gastrointestinal tract is the largest endocrine organ in the body. Gut hormones function to optimize the process of digestion and absorption of nutrients by the gut. In this capacity, their local effects on gastrointestinal motility and secretion have been well characterized. By altering the rate at which nutrients are delivered to compartments of the alimentary canal, the control of food intake arguably constitutes another point at which intervention may promote efficient digestion and nutrient uptake. In recent decades, gut hormones have come to occupy a central place in the complex neuroendocrine interactions that underlie the regulation of energy balance. Many gut peptides have been shown to influence energy intake. The most well studied in this regard are cholecystokinin (CCK), pancreatic polypeptide, peptide YY, glucagon-like peptide-1 (GLP-1), oxyntomodulin and ghrelin. With the exception of ghrelin, these hormones act to increase satiety and decrease food intake. The mechanisms by which gut hormones modify feeding are the subject of ongoing investigation. Local effects such as the inhibition of gastric emptying might contribute to the decrease in energy intake. Activation of mechanoreceptors as a result of gastric distension may inhibit further food intake via neural reflex arcs. Circulating gut hormones have also been shown to act directly on neurons in hypothalamic and brainstem centres of appetite control. The median eminence and area postrema are characterized by a deficiency of the blood-brain barrier. Some investigators argue that this renders neighbouring structures, such as the arcuate nucleus of the hypothalamus and the nucleus of the tractus solitarius in the brainstem, susceptible to influence by circulating factors. Extensive reciprocal connections exist between these areas and the hypothalamic paraventricular nucleus and other energy-regulating centres of the central nervous system. In this way, hormonal signals from the gut may be translated into the subjective sensation of satiety. Moreover, the importance of the brain-gut axis in the control of food intake is reflected in the dual role exhibited by many gut peptides as both hormones and neurotransmitters. Peptides such as CCK and GLP-1 are expressed in neurons projecting both into and out of areas of the central nervous system critical to energy balance. The global increase in the incidence of obesity and the associated burden of morbidity has imparted greater urgency to understanding the processes of appetite control. Appetite regulation offers an integrated model of a brain-gut axis comprising both endocrine and neurological systems. As physiological mediators of satiety, gut hormones offer an attractive therapeutic target in the treatment of obesity.     

Regulation of apoptosis by steroid hormones

Steroid hormones play major roles in regulation of growth, development, homeostasis, and cell death. Together with other hormones and growth factors, steroids regulate both the function and cellular composition of organs throughout the body. In this article we will discuss the mechanisms of steroid hormone regulated apoptosis. Emphasis will be placed on the effect of glucocorticoids on lymphoid cells.     

Relationship between gonadal steroid hormones and vulvar bleeding in southern tamandua, Tamandua tetradactyla

This study aimed at demonstrating the profiles of circulating gonadal steroid hormones during the estrous cycle and pregnancy in a southern tamandua (Tamandua tetradactyla). Additionally, this study clarified the relationship between vulvar bleeding and hormonal changes. The concentrations of serum progesterone (P(4)) and estradiol-17β (E(2)) were determined by enzyme immunoassays. Serum P(4) and E(2) concentrations changed cyclically and the estrous cycle length (± SD) based on the E(2) cycles was 44.3 ± 4.5 days. Vulvar bleeding started to be seen at the decreasing of P(4). The cycle length for vulvar bleeding was 43.3 ± 4.2 days. Interval from the first day of bleeding to the peak of E(2) concentration was 23.1 ± 3.1 days. Serum P(4) during pregnancy remained high and E(2) increased 8 weeks after conception and remained high until parturition. The female delivered normally after a 165 day-pregnancy period and reared the offspring well. Approximately 3 weeks after parturition, serum E(2) and P(4) cycles resumed. Visual bleeding may be useful as a real-time indicator for understanding the ovarian cycle of southern tamanduas, and estrus could be expected approximately 3 weeks after the first bleeding.     

Identification of steroid hormones and fatty acids during gonadal maturation of spiny lobster Panulirus homarus

Information on steroid hormones and fatty acids that play roles in lobster reproduction is still very limited although the data are indispensable to seed production in hatchery. The study was designed to identify steroid hormones and fatty acids during gonadal maturation of spiny lobster (Panulirus homarus). Male spiny lobsters were treated with and without thyroxine injection. Female spiny lobsters were treated with and without eyestalk ablations during mature and immature gonad developments. Androst-5-en-17-one,3β (androst) and estran-3-one,17β (estran), two steroid hormones were identified at different levels of gonadal maturity of spiny lobsters. High concentrations of androst and estran were detected in the male spiny lobsters treated with thyroxine injections. Estran showed high concentrations in female brood stock of spiny lobsters during oogenesis stages both without eyestalk ablation and with ablation of one or two eyestalks, except in the immature female gonads. It was found that stearic acid was the highest and dominant fatty acid in mature male spiny lobster. Stearic acid, oleic acid, palmitic acid and caprylic acid were fatty acids with high concentrations in immature and mature female spiny lobsters. After 30 days in captivity, only stearic acid and oleic acid were found dominantly in eyestalk ablated mature female spiny lobsters.     

Effects of gonadal steroid hormones on hibernation in the Turkish hamster (Mesocricetus brandti)

Summary The Turkish hamster (Mesocricetus brandti) is a photoperiodic species in which exposure to a short day photoperiod induces gonadal atrophy. When hibernating male Turkish hamsters were administered testosterone via subcutaneous silastic capsules hibernation was abruptly terminated. The threshold serum testosterone level required to prevent hibernation was intermediate between the levels observed in males with fully-regressed and fully-functional testes. Dihydrotestosterone was as effective as testosterone in blocking hibernation. Estradiol had a partial inhibitory effect. Progesterone and corticosterone implants had no effect on hibernation. Similar results were obtained in female hamsters. The total period of hibernation for untreated males under laboratory conditions was usually 5–6 months. In most animals testicular growth began to occur toward the end of that period. As gonadal growth continued bouts of torpor decreased in frequency and duration, and hibernation was terminated when the testes approached reproductive size. Castrated males continued to hibernate much longer than intact animals. These observations suggest that in nature decreasing day length in the fall initiates gonadal regression which is followed by cold-induced hibernation. In the spring spontaneous recrudescence of the testes may lead to termination of the dormancy period. This mechanism may enable the species to prepare for the reproductive season with maximum efficiency.Supported by NIH Research Grant HD-10478 and by a grant from the Connecticut Research FoundationThe data in this paper were presented in part at the Annual Meeting of the American Society of Zoologists, Toronto, December 26–30, 1977