Sex hormones and stress in the human male

Six blood samples were obtained from each of a group of 33 healthy males between the ages of 19 and 31, following which radioimmunoassays were used to determine the serum concentrations of testosterone (Tser), 5 alpha-dihydrotestosterone (DHT), and estradiol (E2). In addition, the free testosterone (Tsal) was also measured using saliva samples provided by 23 of the subjects. A questionnaire of our own design was administered together with the Sixteen Personality Factor Questionnaire (16 PF-Test) at the time of the first blood sample in order to check the long-term stress loads of our subjects as well as their abilities to deal with stress. During the investigational period, subjects kept daily records of their sleeping and working hours and noted the appearance of stressful situations. Weather data for Hamburg was also included as a variable in this study. A number of significant relationships between sex hormones and stress could be ascertained; however, it should be kept in mind that the correlation coefficients are low and explain only a small percentage of the variance between the variables. The stress variables "weather condition" and the "Q4" factor of the 16 PF-Test are significantly related to E2 (intersubject correlations). For all samples of all subjects, psychic stress correlates positively with the ratio of Tsal/Tser. There is a significant positive intersubject relationship between Tsal and long-term plus concurrent somatic stress, while somatic stressors on the day preceding a blood and saliva sample (acute somatic stress) correlate positively with Tsal and Tser.     

Sex steroids, pregnancy-associated hormones and immunity to parasitic infection

A wealth of evidence has accumulated that illustrates the ability of sex-associated hormones to influence directly a variety of diverse immunological functions. Thus, it is not surprising that differences have also been noted between the sexes in their relative susceptibility to parasitic infections. Furthermore, during pregnancy, much of the observed maternal immunomodulation, essential for fetal survival, has been attributed to changes in the levels of steroid hormones. These pregnancy-induced alterations in immune function can also have profound effects on the course of parasitic infection. In this article, Craig Roberts, Abhay Satoskar and James Alexander review the immunological basis for differences in the relative susceptibilities of males, non-pregnant females and pregnant females to parasitic infection, particularly leislumaniasis and toxoplasmosis. They also discuss the role of the major sex- and pregnancy-associated hormones in mediating these effects.     

Sex hormones and bone health in males

Sex steroids play a key role in maintaining skeletal integrity lifelong, through a complex variety of endocrine, but also paracrine and possibly autocrine actions. The current knowledge that androgens may act as pro-hormones for estrogens has seriously challenged many traditional views, so that, at least for their skeletal actions, these can no longer be considered exclusively “male” or “female” hormones.     

Thyroid hormones modify susceptibility to lidocaine-kindling in rats.

Lidocaine, a local anesthetic, produces seizures by unknown central mechanisms. The objective of this study was to investigate the effect of cellular metabolism alteration, by changing thyroid hormones levels, on susceptibility to lidocaine-kindling. Lidocaine was administered daily (60 mg/Kg x day, i.p.) to rats treated with thyroxine (300 microg/Kg x day) or methimazole (60 mg/Kg day), dissolved in drinking water. After the 18th lidocaine administration, the cumulative percent of animals convulsed was higher (100%) for the methimazole-treated group and lower (20%) for the thyroxine-treated group, compared to the control group (40%). The results suggest that susceptibility to lidocaine-kindling depends on neuronal metabolism, which probably affects monoamines uptake mechanisms.     

Response of the rat heart to catecholamines and thyroid hormones

Catecholamines and thyroid hormones have a similar influence on heart function and metabolism, but this may occur in a differential manner and to a different extent In this study, the effects of norepinephrine (NE) and of triiodothyronine (T₃) were studied in regard to the function of the left (LV) and right ventricle (RV) and to the oxidative pentose phosphate pathway (PPP). NE was applied in rats as continuous i. v. infusion (0.2 mg/kg/h) for three days. T₃ was given as daily s.c. injections (0.2 mg/kg) for the same period of time. LV, and RV function was measured in the closed-chest trapanal-anesthetized animals using special Millar ultraminature catheter pressure transducers. NE induced an increase in heart rate, in mean arterial pressure, and in total peripheral resistance (TPR). The cardiac RNA/DNA and the left ventricular weight/body weight ratios were increased by about 40%. These effects were prevented by simultaneous -and -receptor blockade with prazosin and metoprolol, respectively, but not by verapamil which abolished the hemodynamic effects. RVSP was significantly elevated by NE in a dose-dependent manner. The functional effects of T₃ on the LV were not as pronounced as those induced by NE. Heart rate and LV dp/dt_max were increased by T₃ and this increase was prevented by concomitant -receptor blockade with, metoprolol. In contrast to NE, T₃ induced an increase in cardiac output and a concominant decrease in TPR. The RNA/DNA ratio was elevated and cardiac hypertrophy had developed after treatment for three days with T₃. These changes were not affected by -receptor blockade with metoprolol. RVSP was increased by T₃ to a lesser extent than with NE. In metabolic terms in turned out that only NE, but not T₃ had a stimulating effect on the cardiac PPP. NE increased the mRNA and activity of glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of this pathway. However, there was no effect of T₃ on G-6-PD activity nor on 6-phosphogluconate dehydrogenase activity, one of the following enzymes in the pathway within the first 5 days of T₃ treatment. These results demonstrate that the functional effects of T₃ were not as pronounced as or even different from those of NE, and that T₃ lacked a stimulating effect on the cardiac PPP.     

Sex hormones influence human cognitive pattern

The major sex differences in cognitive skills are summarized, and the role of sex hormones in early organization and possible maintenance of these differences is discussed. Using animal models and human hormonal anomalies, a good case can be made that prenatal androgens strongly influence adult cognitive pattern, though the relation between baseline androgens and spatial ability, for example, need not be linear. Moreover, men and women remain sensitive to variation in hormonal state, as evidenced in the fluctuations in cognitive and motor performance across natural diurnal, menstrual and circannual rhythms. Evidence from administration of exogenous hormones in humans is more equivocal, though this field ultimately should yield useful information.     

Sex hormones and immune dysregulation in multiple myeloma

A group of 49 multiple myeloma patients, 20 men and 29 women, were evaluated. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-oestradiol (E) and testosterone (T) serum concentrations have been detected by radioimmunoassay. Peripheral blood lymphocyte proliferation in response to phytohaemagglutinin (PHA), concanavalin A (ConA), recombinant interleukin-2 (rIL-2) and dextran sulphate (DxS) was investigated. Our findings provide evidence for two different patterns of sex hormone changes and immune dysfunctions presented differently by male and female multiple myeloma patients. In men increased FSH, LH and E concentrations and an augmented E to T ratio were associated with decreased lymphocyte blastogenic response to PHA, ConA and increased proliferation to rIL-2 and DxS. Female patients with multiple myeloma demonstrated normal values of FSH, LH and T, but a diminished E level and decreased E to T ratio correlated with a lymphocyte normal response to PHA and ConA and augmented blastogenesis to IL-2 and DxS. Our data, while admittedly preliminary, suffice to provide an indication of sex hormone changes in multiple myeloma patients, which could be responsible, at least in part, for the immune dysfunction observed in multiple myeloma.     

Sex hormones, central nervous system and pain

The aim of the present review, which highlights some relationships between sex hormones, the CNS and pain, is to provide reference points for discussion on one of the most intriguing aspects of pain pathophysiology: the presence of sex differences in the response threshold to phasic painful stimuli and in the incidence of chronic pain syndromes. The first part of the review deals with sex steroids and their mechanisms of action. In the second part, the connections between sex steroids, the CNS and pain are illustrated to introduce possible areas of discussion in the study of sex differences in experimental and clinical pain.     

Sex and context: hormones and primate sexual motivation

Gonadal hormones regulate the ability to copulate in most mammalian species, but not in primates because copulatory ability has been emancipated from hormonal control. Instead, gonadal hormones primarily influence sexual motivation. This separation of mating ability from hormonally modulated mating interest allows social experience and context to powerfully influence the expression of sexual behavior in nonhuman primates, both developmentally and in adulthood. For example, male rhesus monkeys mount males and females equally as juveniles, but mount females almost exclusively as adults. Having ejaculated with a female better predicted this transition to female mounting partners than did increased pubertal testosterone (T). It is proposed that increased pubertal T stimulates male sexual motivation, increasing the male's probability of sexual experience with females, ultimately producing a sexual preference for females. Eliminating T in adulthood reduces male sexual motivation in both humans and rhesus monkeys, but does not eliminate the capacity to engage in sex. In male rhesus monkeys the effects of reduced androgens on sexual behavior vary with social status and sexual experience. Human sexual behavior also varies with hormonal state, social context, and cultural conventions. Ovarian hormones influence female sexual desire, but the specific sexual behaviors engaged in are affected by perceived pregnancy risk, suggesting that cognition plays an important role in human sexual behavior. How the physical capacity to mate became emancipated from hormonal regulation in primates is not understood. This emancipation, however, increases the importance of motivational systems and results in primate sexual behavior being strongly influenced by social context.     

High interleukin-4 expression and interleukin-4 gene polymorphisms are associated with susceptibility to human paracoccidioidomycosis

Paracoccidioidomycosis (PCM) is caused by dimorphic fungi fromtheParacoccidioides brasiliensis complex. Previous studies havedemonstrated that the severity of disease is associated with a T-helper 2 immuneresponse characterised by high interleukin (IL)-4 production. In the present study weanalysed two polymorphisms in the IL-4 gene (-590 C/T and intron-3microsatellite) in 76 patients with PCM and 73 control subjects from an endemic area.The production of IL-4 by peripheral blood mononuclear cells after antigen orphytohaemagglutinin stimulation was determined by ELISA. A significant correlationwas observed between the RP2/RP2 intron-3 genotype and infection withParacoccidioides sp. (p = 0.011), whereas the RP1/RP1 genotypewas correlated with resistance. No significant correlation was observed forthe IL-4 promoter polymorphism. Furthermore, the low IL-4expression observed in the control group compared with patients was associated withthe RP1/RP1 genotype. These results suggest that IL-4polymorphismsmight be associated with the ability of the host to control Paracoccidioidessp. infection. The relevance of this polymorphism is supported by theobservation that patients with disease produce high levels of IL-4 following mitogenor antigen stimulation. The IL-4 gene is located in the cytokinecluster region of chromosome 5 where other polymorphisms have also beendescribed.     

Sex hormones in men with coronary arteriosclerosis

Testosterone and estradiol levels were determined in 85 male patients aged between 23 and 52 years with: coronographically diagnosed coronary arteriosclerosis (20 with the instable and 37 with stable coronary disease), and in 28 healthy volunteers serving as a control group. Testosterone concentrations in the instable coronary disease (13.6 +/- 1.7 nM/l) were significantly lower than in the stable form of the disease (18.56 +/- 1.1 nM/l) and in healthy volunteers 20.9 +/- 1.0 nM/l, p less than 0.02 and p less than 0.001 respectively. Estradiol concentrations in male patients with instable coronary disease (228.3 +/- 22.8 pM/l) and with stable form of the disease (157.0 +/- 12.6 pM/l) were significantly higher than in healthy volunteers, p less than 0.02 and p less than 0.001 respectively. The obtained results indicate gonadal disorders in male patients with coronary arteriosclerosis.     

Sex hormones, insulin sensitivity, and diabetes mellitus

Sex differences and the role of gonadal hormones in modulating insulin sensitivity and glucose tolerance are of increasing interest and importance because of the increasing prevalence of type 2 diabetes mellitus and the metabolic abnormalities associated with aging. Body composition is closely associated with insulin sensitivity, and increased body fat, particularly in the visceral compartment, is a risk factor for developing type 2 diabetes mellitus. Sex differences in body composition and/or insulin sensitivity are evident in humans throughout the lifespan. Ovarian hormones influence insulin sensitivity across the menstrual cycle, during pregnancy, and in the menopausal transition. Similarly, estrogens and progestins used for contraception and hormone replacement therapy affect glucoregulation. Nonhuman primates and humans have similar life histories and reproductive characteristics. As a result, nonhuman primates provide a valuable model for investigating factors related to insulin sensitivity. Studies of nonhuman primates have contributed significantly to our understanding of sex differences and the influence of sex steroids in this context. This brief review surveys present knowledge of the sex differences in body composition, insulin sensitivity, and risk for development of type 2 diabetes mellitus derived from studies in humans and nonhuman primates. The influences of endogenous and exogenous gonadal steroids are emphasized.