Non-genomic action of steroids in the nervous system

Past research on the importance of 'soft' neurological signs in schizophrenia has often not examined the relationship between specific groups of neurological signs and different dimensions of schizophrenia psychopathology. Gender differences in the reported relationships have never been explored. In this paper we describe a study of 100 DSM-III-R (65 male and 35 female) schizophrenic patients who were rated for neurological 'soft signs' with the Neurological Evaluation Scale (NES) (1), and for schizophrenic symptomatology with the Scale for Assessment of Negative Symptoms (SANS) and the Scale for Assessment of Positive Symptoms (SAPS). Following a factor analysis of NES items, differential relationships were examined between the five derived NES factors and three well-established dimensions of schizophrenic symptomatology, namely psychomotor poverty, disorganization and reality distortion. Our results failed to show any relationship between NES dimensions and either the reality distortion or disorganization dimensions. There was a modest but differentially significant relationship between psychomotor poverty and an extrapyramidal factor on the NES. This relationship was shown only by male subjects, and was influenced by duration of illness but not by age or neuroleptic medication. On the other hand, female subjects showed a significant relationship between psychomotor poverty and an NES factor reflecting attention and initiative, and between reality distortion and coordination/sequencing of motor activity. These relationships in female subjects were, relative to relationships for male subjects, more independent of the effect of medication and duration of illness.     

Inhaled steroids in asthma

Inhaled steroids are the mainstay of anti-inflammatory treatment of asthma. Topical application of steroids to the asthmatic airway has many benefits as well as potential side effects; however, the side effects are much less prevalent than those caused by the use of chronic oral prednisone.     

Epidural steroids

Although perhaps only controversial internationally, epidural steroids have become the focus of litigation in Australia. The literature provides endorsement but offers little compelling data on rationale and efficacy. Steroid preparations appear to be chemically safe, provided they are accurately injected into the epidural space. Hazards occur if intrathecal penetration is not recognized. Conventional techniques do not guarantee that injectates reach the desired target nerve.     

Pharmacological action of anabolic steroids

Anabolic steroids (AS) are derivatives of androgen (testosterone and its close relatives). AS have been primarily developed for clinical use as anabolic agents with the expectation that they would be relatively less androgenic than testosterone and its close relatives. Various AS are applied to clinical use, but none is free from androgenic activity. Relation between chemical structure and anabolic-androgenic potency of various AS is summarized. AS action in erythropoiesis operates through increased porphyrin formation and production of erythropoietin. Mechanism of AS action in bone formation is suggested that AS potentiate intestinal 1.25(OH)2D receptors. Identification of androgen receptors in normal human osteoblast-like cells suggest that AS act directly on receptor-mediated mechanism. The other action of AS is briefly summarized.     

Metabolism of anabolic androgenic steroids

Anabolic androgenic steroids (AAS) are misused to a high extent in sports by athletes to improve their physical performance. Sports federations consider the use of these drugs in sports as doping. The misuse of AAS is controlled by detection of the parent AAS (when excreted into urine) and (or) their metabolites in urine of athletes. I present a review of the metabolism of AAS. Testosterone is the principal androgenic steroid and its metabolism is compared with that of AAS. The review is divided into two parts: the general metabolism of AAS, which is separated into phase I and phase II metabolism and includes a systematic discussion of metabolic changes in the steroid molecule according to the regions (A-D rings), and the specific metabolism of AAS, which presents the metabolism of 26 AAS in humans.     

Miscellaneous uses of anabolic steroids

The endocrine side effects are mainly androgenic and concern particularly but not exclusively females and children. Depending on individual sensitivity, the dosage used and the androgenicity of the drug concerned, signs of virilization ranging from slight voice disturbances to severe derangement of reproduction can develop, the latter occurring in both sexes. Progestational effects are of little importance. Hepatic alterations are caused almost exclusively by 17 alpha-alkylated steroids and can range from abnormal liver function tests to life-threatening liver tumours. Atherogenic changes in the lipid-lipoprotein balance, again a domain of the 17 alpha-alkylated preparations, might increase the risk of coronary heart disease. The metabolic influences of anabolic compounds can--at excessive dosage levels--create a prediabetic condition and polycythaemia. The influence of anabolic agents on psyche and behavior in normal doses are mostly positive, rendering the drugs useful for adjuvant therapy in patients whose general condition is poor, irrespective of the origin. If given in excessive doses they can cause grave psychic and behavioral disturbances and possibly dependence. Anabolic-androgenic steroids should be used with caution in patients who are particularly sensitive to side effects, where fluid retention must be prevented, in subjects with liver diseases, skeletal metastases of mammary carcinoma, and when longitudinal growth is not completed. They are contraindicated in carcinoma of the prostate and mammary carcinoma in the male and their use should be discouraged in pregnancy and during lactation.     

Regulation of the preovulatory gonadotropin surge by endogenous steroids

Estradiol secreted by growing ovarian follicle(s) has been considered classically to be the neural trigger for the preovulatory surge of gonadotropins. The observation that the estradiol-induced gonadotropin surge in ovariectomized rats is of lesser magnitude and duration than that found in the cycling rat at proestrus has resulted in a search for other steroid regulators. Progesterone is a major regulator of the preovulatory gonadotropin surge. It can only act in the presence of an estrogen background, which is necessary for the synthesis of progesterone receptors. In the estrogen-primed ovariectomized rat, progesterone is able to initiate and enhance the gonadotropin surge to the magnitude observed on the day of proestrus and limit it to 1 day. The physiological role of progresterone in the induction of the preovulatory gonadotropin surge has been demonstrated by the attenuation of the progesterone-induced surge and the endogenous proestrus surge by progesterone receptor antagonist RU486 and the progesterone synthesis inhibitor trilostane. The promoter region of the follicle-stimulating hormone (FHS)-beta gene contains multiple progesterone response elements and progesterone brings about FSH release as well. The reduction of progesterone in the 5 alpha-position appears to be important for the regulation of progesterone secretion. Corticosteroids appear to play a significant role in the secondary FSH surge on late proestrus and early estrus.     

The effect of water-soluble steroids on the cardiovascular system

Water-soluble analogues of steroidal hormones--prednisolone, estradiol, and testosterone on cardiac functional and hemodynamic parameters. Prednisolone and estradiol enhanced myocardial contractility and elevated systemic blood pressure, but testosterone did not affect cardiohemodynamic parameters. Prednisolone showed a drug administration rate-dependent cardiohemodynamic effect.     

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.     

Can gonadal steroids influence cell position in the developing brain?

The preoptic area/anterior hypothalamus (POA/AH) is a site where hormones dramatically influence development. The POA/AH is comprised of multiple subgroups, but little is known about the derivation of these subgroups during development. Results from several laboratories suggest that some cells in the POA/AH originate from progenitor cells in other regions of the developing nervous system. We are exploring pathways for migration in the developing POA/AH in two ways. First, we are examining the distribution of radial glial processes as potential migratory guides using immunocytochemistry. We have identified a transient pattern of radial glial processes from the lateral ventricles to the pial surface at the base of the POA/AH. Additionally, the expression of a molecule in radial glial processes originating in the third ventricle was decreased by prenatal treatment with testosterone. Second, we are utilizing time-lapse video microscopy in vitro to assess the extent and direction of movements of fluorescent dye-labeled cells at different ages in brain slice preparations from the POA/AH of developing rats. Data from these studies indicate that cell migration in the POA/AH includes movements along dorsal-ventral routes and from lateral to medial positions, in addition to the predicted medial to lateral pathway away from the third ventricle. Several researchers have examined effects of gonadal steroids on neurite outgrowth, cell differentiation, cell death, and synaptogenesis. The determination of cell position, however, may be a key event influenced by gonadal steroids earlier in development. The characterization of migratory pathways that contribute to permanent changes in brain structure and ultimately function is essential for unraveling the process of sexual differentiation.     

A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener's granulomatosis

OBJECTIVE: To investigate the effectiveness and side effects of oral versus pulse cyclophosphamide (CYC) in combination with corticosteroids (CS) in the treatment of systemic Wegener's granulomatosis (WG). METHODS: Patients with newly diagnosed systemic WG were enrolled in a prospective, randomized trial. At the time of diagnosis, prior to randomization, every patient received a daily injection of methylprednisolone for 3 days, followed by daily oral prednisone (1 mg/kg/day) and a 0.7-gm/m2 pulse of CYC. Patients were then randomly assigned to receive either prednisone plus intravenous pulse CYC (group A) or prednisone plus oral CYC (group B) as first-line treatment. CYC was given for at least 1 year and was then progressively tapered and discontinued. RESULTS: Fifty patients were included in the study: 27 in group A and 23 in group B. At 6 months, 24 group A patients (88.9%) were in remission, versus 18 group B patients (78.3%). At the end of the trial, 18 group A patients (66.7%) and 13 group B patients (56.5%) were in remission. In group A, 66.7% of the patients experienced side effects, versus 69.6% in group B. Infectious side effects were significantly more frequent in group B (69.6%) than in group A (40.7%) (P < 0.05). The incidence of Pneumocystis carinii pneumonia was higher in oral CYC-treated patients (30.4%) than in pulse CYC-treated patients (11.1%). Nine group A patients (33.3%) and 10 group B patients (43.5%) died. Actuarial curves showed that relapses were significantly more frequent in group A (59.2%) than in group B (13%) (P = 0.02). CONCLUSION: Our results indicate that pulse CYC is as effective as oral CYC in achieving initial remission of WG and is associated with fewer side effects and lower mortality. However, in the long term, treatment with pulse CYC does not maintain remission or prevent relapses as well as oral CYC.     

Current status of oral contraceptive steroids

Recent literature on the status of oral contraceptives (OCs) is reviewed. The steroid composition and relative potency of combined OCs used in the U.S. are set forth, and their mechanism of action is discussed. The effects of OCs on the ovary, myometrium, endometrium, cervix, vagina, breasts, hypothalamus, serum protein levels, carbohydrate metabolism, lipid metabolism, water and electrolyte metabolism, body weight, tryptophan metabolism, vitamins and minerals, the liver, central nervous system, skin, genitourinary tract, gastrointestinal tract, eye, immune system, and on subsequent fertility are reviewed. Factors which should be considered in the choice of an OC are discussed, as well as the time OC use should be initiated in the postpartum and postabortion periods. Contraindications to OC use and considerations in the monitoring of patients are discussed.