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.     

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)     

The effects of oophorectomy and female sex steroids on glucose kinetics in the rat

In the present study, we have analyzed the appearance and maturation of gamma/delta T cells, recognized with a new mAb V65, in the central and peripheral lymphoid organs of fetal, neonatal, and adult Wistar rats. Cytofluorometrical analysis demonstrated the first V65+ gamma/delta T cells in the thymus of 16-17-day embryonic rats, although by immunohistology, they were identified only in 19-day rat embryos in both the cortico-medullary border and thymic medulla. Phenotypically, gamma/delta thymocytes from fetal and neonatal thymus expressed CD3, CD2, and CD5, but only 60-80% were CD8+ and approximately 40-50% expressed the alpha chain (p55) of the IL-2R. In the periphery, the immunohistological study identified for the first time gamma/delta T cells in the splenic white pulp and the gut of 21-day fetal rats, where they occurred within the epithelium as well as in the lamina propria. After birth, gamma/delta lymphocytes appeared in the skin, where they were present as dendritic epidermal T cells in increasing numbers during postnatal life. Whereas these gamma/delta T cells formed the predominant T-cell population in the rat skin, gamma/delta T cells in peripheral lymphoid organs, BALT, or the gut only represented a minor T-cell population. These results are discussed in comparison to gamma/delta T cells of other vertebrate species.     

X chromosome inactivation in carriers of Barth syndrome

Barth syndrome (BTHS) is a rare X-linked recessive disorder characterized by cardiac and skeletal myopathy, neutropenia, and short stature. A gene for BTHS, G4.5, was recently cloned and encodes several novel proteins, named "tafazzins." Unique mutations have been found. No correlation between the location or type of mutation and the phenotype of BTHS has been found. Female carriers of BTHS seem to be healthy. This could be due to a selection against cells that have the mutant allele on the active X chromosome. We therefore analyzed X chromosome inactivation in 16 obligate carriers of BTHS, from six families, using PCR in the androgen-receptor locus. An extremely skewed X-inactivation pattern (>=95:5), not found in 148 female controls, was found in six carriers. The skewed pattern in two carriers from one family was confirmed in DNA from cultured fibroblasts. Five carriers from two families had a skewed pattern (80:20-<95:5), a pattern that was found in only 11 of 148 female controls. Of the 11 carriers with a skewed pattern, the parental origin of the inactive X chromosome was maternal in all seven cases for which this could be determined. In two families, carriers with an extremely skewed pattern and carriers with a random pattern were found. The skewed X inactivation in 11 of 16 carriers is probably the result of a selection against cells with the mutated gene on the active X chromosome. Since BTHS also shows great clinical variation within families, additional factors are likely to influence the expression of the phenotype. Such factors may also influence the selection mechanism in carriers.     

Gonadal steroids have paradoxical effects on brain oxytocin receptors

Specific brain receptors for oxytocin have been described in several mammalian species. The distribution of these receptors differs greatly across species and in the rat, receptor binding in specific brain regions appears to depend upon gonadal steroids. This study used in vitro receptor autoradiography to examine the effects of testosterone on oxytocin receptor binding in the mouse forebrain. Three groups of male mice were compared: castrates treated with blank capsules, castrates treated with testosterone filled capsules, and intact males. Irrespective of steroid treatment, the distribution of oxytocin receptors in mouse forebrain differed markedly from patterns previously described in the rat. In addition to these species differences in receptor distribution, testosterone had effects in the mouse which differed from the induction of receptors previously reported in the rat. In the mouse ventromedial nucleus of the hypothalamus, binding in the untreated castrate males was approximately double that observed in either the intact or the testosterone-treated castrates. In other regions of the mouse brain, such as the intermediate zone of the lateral septum, binding to oxytocin receptors was increased with testosterone treatment. These results suggest that the brain oxytocin receptor varies across species not only in its distribution but also in its regional regulation by gonadal steroids. These apparently paradoxical changes in oxytocin receptor binding may result from either direct or indirect effects of gonadal steroids in mouse brain.     

Effect of sex steroids on the uptake of 3H-leucine by brain tissues of ovariectomized mice

Effect of the sex steroids, progesterone (P) and testosterone (T), on 3H-leucine uptake by the brain cells of ovariectomized mice were examined. Animals were divided into four groups, i.e. group 1: control animals treated with sesame oil; group 2: animals treated with P; group 3: animals treated with T, and group 4: animals first treated with T and then with P. Animals in each group were given a single i.p. injection of 3H-leucine 24 hr after the last hormonal treatment, and sacrificed 2 hr later. Intensity of the uptake of the radiochemical was measured by counting the number of reduced silver grains over cell bodies in various brain regions using an autoradiographic technique. Group 1 showed a relatively high uptake in the SO, PV and SPh when compared with that in the remaining nuclei examined. Groups 2 and 3 both showed a significant enhancement of the uptake in SCH, ARC and PM when compared with that in group 1. Group 4 showed enhancement of the uptake in most of the nuclei except POL, DM and SPH when compared with that in group 1. However, only the POM, PV, SO and VM revealed a significantly higher uptake than the respective nuclei in groups 2 and 3. The uptake by cells in the EC and CC remained unchanged after the hormonal treatment. The present results suggest that in female mice P or T stimulates protein synthesis in the hypothalamic nuclei and that the effect of P on protein synthesis is greatly influenced by T-priming.     

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.     

A new Rett syndrome family consistent with X-linked inheritance expands the X chromosome exclusion map

Although familial recurrences of Rett syndrome (RTT) comprise only approximately 1% of the reported cases, it is these cases that hold the key for the understanding of the genetic basis of the disorder. Families in which RTT occurs in mother and daughter, aunt and niece, and half sisters are consistent with dominant inheritance and variable expressivity of the phenotype. Recurrence of RTT in sisters is likely due to germ-line mosaicism in one of the parents, rather than to recessive inheritance. The exclusive occurrence of classic RTT in females led to the hypothesis that it is X-linked and may be lethal in males. In an X-linked dominant disorder, unaffected obligate-carrier females would be expected to show nonrandom or skewed inactivation of the X chromosome bearing the mutant allele. We investigated the X chromosome inactivation (XCI) patterns in the female members of a newly identified family with recurrence of RTT in a maternal aunt and a niece. Skewing of XCI is present in the obligate carrier in this family, supporting the hypothesis that RTT is an X-linked disorder. However, evaluation of the XCI pattern in the mother of affected half sisters shows random XCI, suggesting germ-line mosaicism as the cause of repeated transmission in this family. To determine which regions of the X chromosome were inherited concordantly/discordantly by the probands, we genotyped the individuals in the aunt-niece family and two previously reported pairs of half sisters. These combined exclusion-mapping data allow us to exclude the RTT locus from the interval between DXS1053 in Xp22.2 and DXS1222 in Xq22.3. This represents an extension of the previous exclusion map.     

Task-related activations in heterotopic brain malformations: a PET study

Positron emission tomography (PET) studies have shown normal or elevated levels of glucose metabolism in neuronal heterotopia, raising the issue of potential participation of heterotopic neurons in cognitive processing. We studied three patients with heterotopic malformations, using [(15)O]water PET and experimental conditions selected according to the location of the malformations. Task performance was associated with blood flow increases of > 17% within the heterotopia in each patient. In two, these occurred in left frontal heterotopia during sentence generation. In the third patient, activations for facial and visuospatial discrimination and picture naming were found in a right posterior heterotopion. Our findings may reflect participation of heterotopia in cognitive function and suggest that heterotopic neurons synapse with neurons in other brain regions.     

A prospective, double-blind, randomized study of the effects of perioperative steroids on palatoplasty patients

OBJECTIVE: To determine whether perioperative steroids affect the outcome of patients who undergo palatoplasty. DESIGN: A prospective, double-blind, randomized study. SETTING: A university medical center. PATIENTS: Twenty patients undergoing primary repair of a cleft palate. INTERVENTION: A prospective double-blind technique was used to randomly assign patients to receive a placebo or dexamethasone sodium phosphate perioperatively. MAIN OUTCOME MEASURE: Patients were monitored for postoperative airway distress, fever, oral fluid intake, days of hospitalization, and wound healing. RESULTS: The use of perioperative steroids was associated with shorter hospitalizations. No adverse sequelae from the administration of steroids were identified. CONCLUSIONS: In our current managed care environment, the use of perioperative steroids may play an important role in reducing health care costs.     

A meta-analysis of sex differences in the effects of unilateral brain damage on intelligence test results.

Linear regression analyses were used to examine 16 studies on the effect of unilateral brain damage on WAIS IQ. Although only 2 of these studies had originally been designed to investigate sex differences, analyses revealed that the proportions of males and females tested had affected the overall outcome. A greater preponderance of men in either the left- or right-lesion groups was associated with larger test-specific deficits in the Verbal and the Performance Scales, respectively. Left-lesioned women showed an impairment on both scales, perhaps because women may use left-hemisphere processing to solve both verbal and ostensibly nonverbal problems. (French abstract) (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

A case of syndrome X

Type 2 diabetes is increasing in prevalence and is predominantly managed in general practice. This series contains case histories which deal with some of the metabolic problems that may be encountered in the management of these patients and indicates some of the many issues, other than glycaemic control, that need to be considered.