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At least 127 records · Page 7Linked to original sources
PubMed2006

Sex-specific determinants of serum adiponectin in older adults: the role of endogenous sex hormones.

OBJECTIVE: To assess the sex-specific association of adiponectin with multiple factors thought to influence its levels, with a special emphasis on endogenous sex hormones. DESIGN AND METHODS: A cross-sectional study of determinants of serum adiponectin in 873 men and 673 postmenopausal women, ages 50-92. Factors evaluated include age, body size, fat distribution, lifestyle (exercise, smoking, alcohol intake), insulin resistance, renal function and endogenous sex hormone levels (total and bioavailable testosterone and estradiol). RESULTS: Median serum adiponectin was 50% higher in women than men (P<0.001). In unadjusted analyses, adiponectin was positively related to age, alcohol intake, high-density lipoprotein (HDL) and testosterone, and negatively related to waist girth, body mass index, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), triglycerides and bioavailable estradiol in both sexes (all P<0.01). Adiponectin was positively related to blood urea nitrogen, a measure of renal function, in men only (P<0.001). Sex-specific multivariate linear regressions adjusting for HDL and triglycerides showed that only age, HOMA-IR and sex hormones independently predicted circulating adiponectin for both men and women. Higher levels of endogenous testosterone and lower bioavailable estradiol concentrations each predicted higher adiponectin; this was true for both sexes, and was not explained by differences in age, adiposity, alcohol intake, insulin resistance or lipoprotein levels. CONCLUSIONS: The association of adiponectin with the factors studied here is strikingly similar for men and women. Sex differences in circulating adiponectin levels in older adults cannot be explained by sex hormone regulation.

Adiponectin↗
PubMed2001

Sex hormones and chronic headache in women.

Women experience changes in headache pattern in relation to changes in their reproductive cycles. Menarche, menses, pregnancy, menopause and the use of exogenous oestrogen-containing medications frequently alter baseline headache patterns. Changing patterns of headache in women may be linked to alterations in levels of sex hormones. Sex hormones directly influence headache by affecting the activity of a variety of neurochemicals important for headache, including serotonin (5HT). Treating headache alterations in women may include therapies that modify sex hormones or neurochemicals.

Cerebrovascular Circulation↗
PubMed1997

Cross genotype sex hormone treatment in two cases of hypogonadal osteoporosis.

BACKGROUND: Sex hormone deficiency is the most common cause of bone loss. Reduced bone mass and an increased risk for osteoporotic fractures have been described in hypogonadal subjects of both sexes. We present here the results of treating two patients showing abnormal sexual differentiation (an XX male and an XY female), who suffered from bone loss related to sex hormone deficiency, with cross genotype sex hormones. SUBJECTS AND METHODS: Patient 1 was an asymptomatic 39-yr-old XY female with complete androgen insensitivity. Her testes had been removed, and she later discontinued estrogen treatment. Patient 2, a 37-yr-old XX male, had congenital adrenal hyperplasia, which led to a masculine phenotype. He was ovariectomized and reared as a male. He was treated with glucocorticoids but refused androgen treatment for many years. We treated both patients with phenotypically matched sex hormones (patient 1 received conjugated estrogens 1.25 mg/day, and patient 2 received 250 mg testosterone every 4 weeks) and followed their bone mineral density (BMD) using dual-energy X-ray absorptiometry, urine calcium, and hydroxyproline excretion. RESULTS: Before treatment both patients had low sex hormones and highly elevated gonadotropins. As a result of treatment urine hydroxyproline excretion decreased from 45 and 26.7 mg/g creatinine to 15 and 15.9 mg/g creatinine in patients 1 and 2 respectively. In patient 1, lumbar BMD rose from 0.912gr/cm2 to 0.976gr/cm2 and femoral neck BMD rose from 0.716gr/cm2 to 0.836gr/cm2 after 4 years of treatment. In patient 2, lumbar BMD rose from 0.717gr/cm2 to 0.815gr/cm2 and the femoral neck BMD rose from 0.509gr/cm2 to 0.635gr/cm2 after 27 months of treatment. CONCLUSIONS: Phenotypically-matched sex hormone therapy in patients with abnormal sexual differentiation is essential not only to maintain external appearance but also for the preservation of bone mass.

Adult↗
PubMed2005

Handedness, functional cerebral hemispheric lateralization, and cognition in male-to-female transsexuals receiving cross-sex hormone treatment.

This study examined the impact of sex hormones on functional cerebral hemispheric lateralization and cognition in a group of male-to-female transsexuals receiving cross-sex hormone therapy compared to eugonadal men with a male gender identity. Cerebral lateralization was measured with a handedness questionnaire and a visual-split-field paradigm and cognitive tests sensitive to sex hormone exposure (identical pictures, 3-D mental rotation, building memory) were also administered. Endocrine measures on the day of participation for transsexual and control subjects included total testosterone, free testosterone, estradiol, gonadotropins, and sex hormone binding globulin concentrations. Compared to controls, male-to-female transsexuals had elevated estradiol and sex hormone binding globulin concentrations and suppressed testosterone concentrations. Transsexual subjects showed a trend toward less exclusive right-handedness than controls. No group differences were observed on the visual-split-field or cognitive tasks. No direct associations were observed between endocrine measures and the laterality measures and cognitive performance. Previous observations of female-typical patterns in cerebral lateralization and cognitive performance in male-to-female transsexuals were not found in the current study.

Adult↗
PubMed2003

Relationship of leptin and sex hormones to bone mineral density in men.

Sex hormones are strongly associated with bone mineral density (BMD) in adult humans. Leptin, a hormonal product of the OB gene, also appears to be associated with BMD, but results from previous studies are conflicting. Most of the studies in this area have been in women and apparently none have simultaneously analyzed the relationship of estradiol, testosterone, and leptin with BMD in healthy men. To address these issues, serum sex hormones, sex-hormone-binding globulin (SHBG), leptin, dehydroepiandrosterone sulfate (DHEAS), and insulin were measured in 50 apparently healthy men, 18-66 years of age. After controlling for age and body mass index (BMI), BMD correlated positively with estradiol ( p=0.007) and testosterone ( p=0.019), but negatively with leptin ( p=0.001). No significant correlations between BMD and SHBG, DHEAS, or insulin were observed. In multiple regression analysis with age, BMI, estradiol, testosterone, and leptin as the independent variables, only age ( p<0.05), BMI ( p<0.001), and leptin ( p=0.004) were significantly related to BMD. These findings suggest that in men, leptin may have an important negative relationship with BMD.

Adolescent↗
PubMed2003

Effect of sex hormones on experimental autoimmune uveoretinitis (EAU).

PURPOSE: Sex hormones have been associated with the prevalence, susceptibility, and severity of autoimmune disease. Although the exact mechanism is unknown, sex hormones are reported to influence cytokine production, specifically by affecting the balance of Th1 and Th2 effector cells. We evaluated the effect of estrogen, progesterone, and testosterone in autoimmune uveoretinitis (EAU), a rodent model of human ocular autoimmune disease. METHODS: Lewis rats implanted with either beta-estradiol (estrogen), 5-dihydrotestosterone (5-DHT), norgestrel (progesterone), or estrogen plus progesterone were immunized with the retinal antigen interphotoreceptor retinoid binding protein (IRBP) peptide. Evaluation of EAU was based on histology of the eyes and measurement of peripheral immunological responses of DTH and lymphocyte proliferation to S-antigen. Quantitative RT-PCR was used to measure IFN-gamma and IL-10 mRNA in the eyes. RESULTS: In female rats 5-DHT significantly decreased, estrogen slightly enhanced, but progesterone or estrogen + progesterone did not affect EAU. In contrast, in male rats 5-DHT slightly decreased, estrogen moderately decreased, progesterone did not effect, but, estrogen + progesterone slightly decreased EAU. The results correlated with the ocular levels of Th1 (IFN-gamma) and Th2 (IL-10) cytokine messengers. CONCLUSION: The data support the hypothesis that sex hormones may affect autoimmune diseases by inducing changes in the cytokine balance. This suggests that sex hormone therapy could be considered as an adjunct to anti-inflammatory agents to treat ocular autoimmune diseases in humans.

Animals↗
PubMed1978

Effect of anticonvulsants on plasma testosterone and sex hormone binding globulin levels.

Plasma sex hormone binding globulin (SHBG) and testosterone levels were measured in 29 patients with epilepsy (16 men and 13 women), most of them on chronic therapy with anticonvulsant drugs. Sex hormone binding globulin concentrations were increased in both sexes and testosterone levels in male patients. It is postulated that anticonvulsants may induce hepatic synthesis of SHBG.

Anticonvulsants↗
PubMed1997

Sex hormones and the thymus in relation to thymocyte proliferation and maturation.

This paper reviews the mechanism of sex hormone actions on the thymus, presenting mainly our data obtained at the cellular and molecular levels. First, data supporting the "genomic" action via the nuclear sex hormone receptor complexes are as follows: 1) sex hormone receptors and the thymic factor (thymulin) are co-localized in thymic epithelial cells, but not in T cells; 2) production/expression of thymic factors (thymulin, thymosin alpha 1) are remarkably inhibited by sex hormone treatment; 3) sex hormones cause changes in T cell subpopulations in the thymus; and 4) sex hormones strongly influence the development of thymus tumors in spontaneous thymoma BUF/Mna rats through their receptor within the tumor cells. Secondly, data indicating the "non-genomic" action of sex hormones via a membrane signal-generating mechanism are as follows: 1) the proliferation/maturation of thymic epithelial cells is mediated through protein kinase C activity introduced by sex hormones; 2) sex hormones directly influence DNA synthesis and cdc2 kinase (cell cycle-promoting factor) activity.

Animals↗
PubMed1991

Sex hormone changes in post-menopausal women with primary biliary cirrhosis (PBC) and with cryptogenic chronic liver disease.

Sex hormones and sex hormone binding globulin (SHBG) have been studied in 32 female post-menopausal patients (16 with Primary Biliary Cirrhosis (PBC) and 16 with cryptogenic chronic liver disease (CLD). Dehydroepiandrosterone-sulfate (DHEA-S) serum levels were significantly higher in PBC compared to CLD subjects (p less than 0.005). In PBC DHEA-S concentration was higher in precirrhotic than in cirrhotic patients (p less than 0.02). SHBG was raised in both PBC and CLD patients but higher in CLD compared to PBC subjects (p less than 0.002). PBC reveals a sex hormone pattern similar to post-menopausal subjects with breast cancer. These results suggest that sex hormone alteration is present in females with different types of liver disease, but the metabolic pattern is not due to liver disease per se.

Aged↗
PubMed2003

Relationships in men of sex hormones, insulin, adiposity, and risk factors for myocardial infarction.

That sex hormones, insulin, and obesity all correlate with the constellation of risk factors for myocardial infarction (MI) that has come to be known as "syndrome X," the "insulin-resistance syndrome," or the "metabolic syndrome" suggests that any one or more of them could underlie and link the risk factors to form the constellation. That sex hormones, insulin, and obesity also correlate with each other complicates their identification as an underlying link. To compare the likelihood of each being a link, we measured and determined the interrelationships of sex hormones, insulin, adiposity variables, and risk factors for MI in 80 apparently healthy men. Of the adiposity variables, visceral adipose tissue (VAT) correlated more strongly with the risk factors for MI than did body mass index (BMI), total adipose tissue (TAT), subcutaneous adipose tissue (SCAT), waist-to-hip ratio (WHR), and waist circumference (W). Controlling for VAT eliminated all of the other adiposity correlations that had been significant. VAT, therefore, was used as the measure of adiposity for further data analysis. VAT correlated more strongly with risk factors for MI than did sex hormones and insulin, and most of the correlations of sex hormones and insulin with risk factors for MI lost statistical significance after controlling for VAT. Testosterone and the ratio of estradiol-to-testosterone (E/T) correlated with insulin; on controlling for VAT, only the E/T-insulin correlation remained significant (r =.38, P <.001) and on multiple linear regression analysis, insulin was associated with estradiol (P =.01) and testosterone (P =.04) independently of VAT and age. In conclusion, (1) VAT in men may largely explain the correlations of sex hormones, insulin, and obesity with the risk factors for MI measured, (2) VAT may be the principal factor in men, independently of other measures of adiposity, that links risk factors for MI to form the constellation, and (3) estradiol may play a more important role in the sex hormone-insulin relationship in men than has generally been considered.

Adipose Tissue↗
PubMed1997

Interrelationships between weight loss, body fat distribution and sex hormones in pre- and postmenopausal obese women.

OBJECTIVES: Relationships between regional body fat distribution and sex hormones as well as changes in sex hormones after weight loss were evaluated. SETTING: All subjects were hospitalized in the Institute of Internal Medicine of the University of Verona. SUBJECTS: Twenty-six premenopausal (age 33.7 +/- 10.2 years) and 15 postmenopausal (age 57.9 +/- 5.9 years) obese women. INTERVENTIONS: Body weight, body-mass index, waist and hip circumferences, visceral fat by computed tomography and sex hormones were evaluated before and after 4 weeks on a very low energy diet. RESULTS: Body-mass index was higher in pre-than in postmenopausal women, although the difference was not significant. Total and free testosterone were significantly higher in the pre- than in the postmenopausal group (P < 0.001). Significant negative correlations were found between age and total testosterone (r = -0.65; P < 0.001), free testosterone (r = -0.54; P < 0.001), androstenedione (r = -0.46; P < 0.01) and urinary cortisol excretion (r = -0.50; P < 0.01). A negative correlation was found between visceral fat and total testosterone (r = -0.41; P < 0.01). After adjusting for age, the negative correlation between total testosterone and visceral fat encountered both in the subject group as a whole and in premenopausal women was no longer significant, whilst a significant negative association between visceral fat and sex hormone binding globulin (SHBG) (r = -0.56; P < 0.001) was always found. When step-down regression analysis was used to evaluate the joint effect of age, menopausal status, and anthropometric and metabolic variables on sex hormones, age was the most powerful independent variable for predicting total testosterone, free testosterone and androstenedione levels, whilst menopausal status was the most powerful predictor of FSH and LH levels. Changes in hormones after VLED were analysed separately in pre- and postmenopausal women. None of the hormones changed significantly after VLED in the postmenopausal group, except for FSH values. LH, free testosterone and urinary cortisol excretion values decreased significantly after VLED in the premenopausal group. CONCLUSIONS: Our data show that age, to a greater extent than visceral fat, seems to be negatively associated with steroid sex hormones. Weight loss seems to be associated with changes in sex hormones only in premenopausal women.

Adolescent↗
PubMed2000

Sex hormones and headache.

The normal female life cycle is associated with a number of hormonal milestones: menarche, pregnancy, contraceptive use, menopause, and the use of replacement sex hormones. Menarche marks the onset of menses and cyclic changes in hormone levels. Pregnancy is associated with rising noncyclic levels of sex hormones, and menopause with declining noncyclic levels. Hormonal contraceptive use during the reproductive years and hormone replacement in menopause are therapeutic hormonal interventions that alter the levels and cycling of sex hormones. These events and interventions may cause a change in the prevalence or intensity of headache. The menstrual cycle is the result of a carefully orchestrated sequence of interactions between the hypothalamus, pituitary, ovary, and endometrium, with the sex hormones acting as modulators and effectors at each level. Estrogen and progestins have potent effects on central serotonergic and opioid neurons, modulating both neuronal activity and receptor density. The primary trigger of Menstrually-related migraine (MM) appears to be the withdrawal of estrogen rather than the maintenance of sustained high or low estrogen levels. However, changes in the sustained estrogen levels with pregnancy (increased) and menopause (decreased) appear to affect headaches. Headaches associated with OC use or menopausal hormonal replacement therapy may be related, in part, to periodic discontinuation of oral sex hormone preparations. The treatment of migraine associated with changes in sex hormone levels is frequently difficult and the patients are often refractory to therapy. Based on what is known of the pathophysiology of migraine, we have attempted to provide a logical approach to the treatment of headaches that are associated with menses, menopause, and OCs using abortive and preventive medications and hormonal manipulations. Considerable evidence suggests a link between estrogen and progesterone, the female sex hormones, and migraine. (Silberstein and Merriam, 1997; Lipton and Stewart, 1993; Epstein et al., 1975; Goldstein and Chen, 1982; Selby and Lance, 1960) Although no gender difference is apparent in prepubertal children, with migraine occurring equally in 4p. 100 of boys and girls, (Goldstein and Chen, 1982, Waters and O'Connor, 1971) migraine occurs more frequently in adult women (18p. 100) than in men (6p. 100). (Lipton and Stewart, 1993) Migraine develops most frequently in the second decade, with the peak incidence occurring with adolescence. (Selby and Lance, 1960; Epstein et al., 1975) Menstrually-related migraine (MM) begins at menarche in 33p. 100 of affected women (Epstein et al. , 1975). MM occurs mainly at the time of menses in many migrainous women, and exclusively with menses (true menstrual migraine [TMM]) in some (Epstein et al., 1975). Menstrual migraine can be associated with other somatic complaints arising before and often persisting into menses, such as nausea, backache, breast tenderness, and cramps and like them appears to be the result of falling sex hormone levels (Silberstein and Merriam, 1997; American Psychiatric Association, 1994). In addition, premenstrual migraine can be associated with premenstrual dysphoric disorder (PDD), also called "premenstrual syndrome" (PMS), which is distinct from the physical symptoms of the perimenstrual period and is probably not directly driven by declining progesterone levels (Mortola, 1998). Migraine occurring during (rather than prior to) menstruation is usually not associated with PMS (Silberstein and Merriam, 1997). Migraine may worsen during the first trimester of pregnancy and, although many women become headache-free during the last two trimesters, 25p. 100 have no change in their migraine (Silberstein, 1997). MM typically improves with pregnancy, perhaps due to sustained high estrogen levels (Silberstein, 1997). Hormonal replacement with estrogens can exacerbate migraine and oral contraceptives (OCs) can change its character and frequency

Adult↗
PubMed2002

The sex hormone receptors in the bladder in childhood - I: preliminary report in male subjects.

The sex hormone receptors (oestrogen, androgen, progesterone) in the bladder were demonstrated in clinical studies by various authors in adult patients. But the presence of these receptors in childhood had not been investigated. The aim of this study was to assess the presence of sex hormone receptors in the bladder of male subjects in childhood. The study included 20 bladder biopsies from a total of 15 children. Biopsies were taken during open surgery and/or cystoscopic procedures for various indications from the bladder dome, trigonum and in the region of the bladder neck. All biopsies were routinely fixed and processed for histopathological assessment and investigated immunohistochemically to determine the sex hormone receptors in the bladder. The sex hormone receptors were demonstrated with different densities and locations. In particular, sex hormone receptors were found very frequently in biopsies taken from the bladder neck. Overall receptor positivity in the specimens was 90 % for progesterone, 65 % for androgen and 25 % for oestrogen. There was no receptor expression in the deeper tissues of the bladder wall. This preliminary study demonstrated: 1. Sex hormone receptors are present in children; 2. There was a female sex hormone (progesterone, oestrogen) receptor expression in male subjects; 3. The receptors are mainly localised at the bladder neck and in transitional epithelium of the bladder wall. We think that the sex hormone receptor map may be useful in the evaluation of lower urinary tract and specially bladder neck disorders in childhood in the future.

Biopsy↗
PubMed1992

Regulation of the mouse liver cytochrome P450 2B subfamily by sex hormones and phenobarbital.

The sex-dependent expression and inducibility of the cytochrome P450 2B subfamily was studied in DBA/2 and Balb/c mice, and their F1 recombinants, at the mRNA, protein and activity levels. Analysis of poly(A)+ RNA with specific oligonucleotide probes directed to known mRNAs within the mouse 2B subfamily revealed that the levels of P450 2b-10 and 2b-9 mRNAs were co-regulated with two proteins (56 and 53 kDa) detected by a 2B-specific polyclonal antibody. Other mRNAs related to the 2B subfamily were barely or not at all detectable, and did not coincide with protein expression, suggesting that P450s 2b-9 and 2b-10 are the major 2B isoenzymes present in mouse liver. Specifically, castration of males increased the expression of 2b-9 and 2b-10 mRNAs and protein up to female levels, and testosterone administration to castrated mice reversed these changes. Ovariectomy of females appears to increase the expression of these P450s slightly. 2b-10, but not 2b-9, mRNA and protein were induced by phenobarbital. Based on immunoinhibition studies and the levels of these isoenzymes, P4502b-10 appears to be the major catalyst of 7-pentoxyresorufin O-dealkylation. Both P4502b-9 and P4502b-10 contribute up to 30% of the testosterone 16 alpha-hydroxylation, the balance being catalysed by P450s within the 2D subfamily. These experiments show that the female-predominant expression of the two mouse liver isoenzymes P4502b-9 and P4502b-10 is dependent on sex hormones. The fact that P4502b-9 does not respond to phenobarbital, while P4502b-10 is regulated by both phenobarbital and sex hormones, demonstrates the complexity of P450 expression even within one subfamily.

Amino Acid Sequence↗
PubMed1985

Binding of steroid hormones and anabolic agents to bovine sex-hormone binding globulin.

Binding of some selected steroids and anabolic agents to bovine sex-hormone binding globulin (SHBG) was investigated. SHBG binding affinities, relative to the reference hormone 5 alpha-dihydrotestosterone, were estimated for the compounds. The results demonstrate that binding of steroid hormones to SHBG is facilitated by the 17 beta-hydroxyl group, possibly involving hydrogen binding, and by the methyl group at C-19 of the steroid moiety. Structural modifications at C-17 of a steroid molecule involving esterification, epimerization or reduction of the 17 beta-hydroxyl group, or introduction of a bulky 17 alpha group have the effect of decreasing the SHBG binding affinity of the steroid molecule.

Androstenedione↗
PubMed2025

Amino acid profiles, aging, and sex hormone interactions in the elderly Iranian population: a metabolomics study.

BACKGROUND: Aging and sex hormones significantly influences on metabolic profiles, particularly in individuals aged 50 year and older. This study aimed to investigate the associations between serum metabolites, aging, and sex hormone levels among elderly individuals in Bushehr, Iran - a coastal region characterized by a unique lifestyle, dietary patterns, and environmental conditions, such as high seafood consumption and exposure to marine climate, which may collectively influence metabolic profiles and hormone levels in the aging population. METHODS: This cross-sectional study analyzed data from the Bushehr Elderly Health Program, which included 2001 participants (1143 women and 858 men) aged over 50 years old from Bushehr, Iran. Serum levels of 20 amino acids were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the results were analyzed based on gender, age, menopause status, menopause age, and serum levels of sex hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol (E2). Statistical analyses were performed using SPSS version 25.0 and R version 4.0.3, with a focus on gender differences and the correlation between aging, sex hormones, and metabolite profiles. RESULTS: Among the 2001 participants, mean ages were 61.57&#x2009;&#xb1;&#x2009;7.6 years for women and 62.92&#x2009;&#xb1;&#x2009;8.4 years for men. Men had higher serum levels of glutamic acid, leucine, methionine, phenylalanine, tyrosine, valine, citrulline, ornithine, proline, threonine, histidine, lysine, tryptophan, asparagine, and glutamine, while women had higher levels of glycine and serine. Aging was associated with notable changes in amino acid levels, such as increased citrulline and decreased threonine in women, and similar trends in men with a pronounced decrease in alanine. In men, low testosterone levels were linked to reduced concentration of alanine, methionine, phenylalanine, tyrosine, citrulline, glycine ornithine, serine, lysine, asparagine, and glutamine. Postmenopausal women showed a significant decrease in threonine levels. DISCUSSION: The findings highlight the complex interplay between aging, sex hormones, and metabolic changes. Gender-specific differences in amino acid profiles suggest that sex hormones play a pivotal role in modulating metabolism, which may influence susceptibility to metabolic disorders. These insights could inform the development of targeted interventions tailored to the specific needs of aging populations. Future research should investigate the underlying mechanisms linking sex hormones to metabolic pathways and assess their potential for improving health outcomes in older adults.

Aging↗
PubMed1994

Sex hormone modulation of neural development in vitro.

The sex hormonal milieu during human and primate development is thought to influence adult cognition, perception, and behavior. Similarly in the rat, the neonatal sex hormonal milieu dictates adult behavior, as well as patterns of neural organization within the CNS. Specifically, estrogen and androgen alter neurite outgrowth, neuritic spine development, and synaptogenesis in the limbic system and spinal cord. To examine specific molecular/cellular effects of sex hormones on neurons, in vitro models were developed, using the PC12 cell line. Wild-type cells (PC12-WT) were stably transfected either with an expression vector coding for the human estrogen receptor (ER), androgen receptor (AR), or with a control vector. Resultant clones were isolated, screened for incorporation of vector and expression of ER or AR mRNA and protein, and analyzed for morphologic responses to estrogen and androgen, respectively. PC12-WT, NEO9 (ER-negative, AR-negative), SER8 (ER-positive, AR-negative), and AR8 (ER-negative, AR-positive) cells were exposed to nerve growth factor and graded doses of estradiol or dihydrotestosterone (DHT) for 2 days. In SER8 cells, estradiol led to dose-dependent increases in the frequency of neurite outgrowth, spine development, and interneuritic connectivity. Estradiol increased the frequency of gap junction frequency and length, and functional dye-coupling in SER8 cells. Conversely, in AR8 cells, DHT induced a dose-dependent increase in mean neurite length, branch order, and neuritic field area, while neurite branch segment length and soma area were unaffected. These results suggest that SER8 and AR8 cells in vitro recapitulate various sex hormonal effects on neurons in vivo. Estrogen and androgen appear to induce inherent neural morphologic programs in which androgen increases neurite arborization and the receptive field of individual cells, increasing the likelihood for intercellular communication, while estrogen actually induces this communication, in the form of spines, synapses, and gap junctions. Thus estrogen and androgen act in different but complementary ways to modulate neural development and organization.

Androgens↗