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David J Handelsman

Publications and source records attributed to David J Handelsman.

At least 37 records · Page 2Linked to original sources
PubMed2005

Molecular cloning and characterization of a novel androgen repressible gene expressed in the prostate epithelium.

Prostate cancer deaths are due to functional escape of prostate cancer cells from their original androgen-dependent growth. To better understand the origin and evolution of hormone-refractory prostate cancer, it is important to identify and characterize genes expressed in the androgen-deprived prostate. We have verified that the rudimentary prostate of congenital androgen deficient mice (hpg) is indeed androgen independent. Using suppression subtractive hybridization between mRNA derived from prostates of hypogonadal (hpg) with or without 14 days of testosterone replacement we have cloned a novel gene from the hpg prostate, termed ADMP (for androgen down regulated gene expressed in mouse prostate), that is down regulated by androgens. ADMP expression is strong in hpg mouse prostate, weak in mature castrated mouse prostate and absent in normal intact or androgen-replaced hpg mouse prostates. While ADMP expression is androgen independent in the hpg prostate, it appears to be androgen-dependent in the kidney and brain of normal intact mouse suggesting tissue specific regulation of ADMP by androgens. Human ADMP mRNA expression is suppressed by androgens in the androgen-sensitive LNCaP cell line. The predicted mouse and human protein of 76 amino acids shares sequence similarity to a putative G-protein coupled receptor indicating its possible role in signal transduction. Human ADMP expression was seen predominantly in the prostate epithelium with weaker expression in the fibroblasts and endothelial cells. Cloning and characterization of ADMP has made it feasible to determine its prospective role in the absence of androgens in prostate cancer.

Adrenalectomy↗
PubMed2005

Andropause: invention, prevention, rejuvenation.

There is a growing interest, as well as a booming industry, in the use of testosterone therapy for middle-aged and older men. This interest has led to the definition of a new condition, termed 'andropause', meaning the putative somatic consequences of gradually falling blood testosterone concentrations during male aging. This trend risks replicating both the rejuvenation fads of a century ago and the recent experience in estrogen therapy for menopause that has been propelled for decades by advocacy substituting for reliable scientific evidence. The current status and prospects for androgen therapy in middle-aged and older men should be evaluated critically from the perspective of male reproductive health during aging. This review appraises current knowledge with a focus on the questionable basis for using androgen therapy to improve male reproductive health during aging.

Androgens↗
PubMed2005

Androgen receptor gene expression in leucocytes is hormonally regulated: implications for gender differences in disease pathogenesis.

OBJECTIVE: There is evidence that male sex hormones influence the rate of progression of inflammatory and cardiovascular diseases. We have previously shown that human leucocytes and arterial cells isolated from male donors express more androgen receptor (AR) than those from female cells, with potentially pro-atherogenic effects. We now investigate whether the gender difference in AR expression is due to genetic or hormonal regulation. DESIGN AND PATIENTS: The influence of hormones on AR expression were studied in hpg mice (a mouse model of androgen deficiency) treated with testosterone, oestradiol or dihydrotestosterone (DHT). Blood samples were obtained for leucocyte AR expression and hormone levels from 53 subjects, grouped into: 12 male [six young adult (27-45 years), six elderly (71-79 years)] and six female (young adult 25-45 years) healthy controls; six male-to-female transsexuals (M2F; 20-50 years) receiving stable pharmacological oral oestrogen treatment; six female-to-male transsexuals (F2M; 31-51 years) receiving stable androgen replacement therapy; five younger men (18-56 years) who had been receiving long-term androgen replacement therapy for hypogonadal disease; six elderly men (72-88 years) who had undergone medical castration for prostate cancer treatment; and 12 male bone marrow transplant recipients (BMT; 23-65 years) from either male or female donors. MEASUREMENTS: Serum testosterone and oestradiol concentrations were measured by established immunoflurometric assays from unextracted human serum. AR mRNA levels were measured by RT-PCR and AR protein levels by western blot (cell culture) or immunohistochemistry (mouse arteries). RESULTS: We found that AR mRNA levels were significantly down-regulated in the leucocytes of hpg mice that were treated with exogenous testosterone, oestradiol or DHT. AR protein levels were also lower in aortic tissue from the same mice. In humans, we found AR expression was significantly down-regulated by exogenous treatment with testosterone in F2M (31 +/- 13%, compared with control) or oestradiol in M2F (22 +/- 5%) but was significantly up-regulated by endogenous testosterone in BMT (128 +/- 17%). Low androgen levels measured in castrated older men were associated with markedly increased AR expression (207 +/- 26%, P < 0.05) compared with age-matched older male controls (100 +/- 2%). CONCLUSIONS: Our results indicate a regulated ability of vascular cells to respond to sex hormones, with the effects of exogenous therapies differing markedly from those due to endogenous sex hormones. We conclude that the gender difference in AR expression in vascular cells is hormonally, rather than genetically, controlled.

Adult↗
PubMed2005

Transgenic models for exploring gonadotropin biology in the male.

Unraveling the selective actions of the two pituitary- derived gonadotropins FSH and LH in vivo is complicated by their very close structural and functional similarities, and their coordinate regulation. Both gonadotrophins are composed of a common alpha-subunit and distinct beta-subunits, which are simultaneously secreted as heterodimers in response to a single trophic hormone GnRH. Functionally, gonadotrophins interact with related receptors and share the same ultimate cellular site in the testis, the Sertoli cell with receptors for both FSH and the androgens synthesized in response to LH. This article will review the strategies to overcome these intimate connections and discuss key findings from trans-genic models developed to study gonadotropin actions in the male.

Animals↗
PubMed2005

Empirical estimation of free testosterone from testosterone and sex hormone-binding globulin immunoassays.

BACKGROUND: The growing interest in measuring blood free testosterone (FT) is constrained by the unsuitability of the laborious reference methods for wider adoption in routine diagnostic laboratories. Various alternative derived testosterone measures have been proposed to estimate FT from either additional assay steps or calculations using total testosterone (TT) and sex hormone-binding globulin (SHBG) measured in the same sample. However, none have been critically validated in large numbers of blood samples. METHODS: We analyzed a large dataset comprising over 4000 consecutive blood samples in which FT as well as TT and SHBG were measured. Dividing the dataset into samples with blood TT above and below 5 nM, using a bootstrap regression modeling approach guided by Akaike Information Criterion for model selection to balance parsimony against reduction of residual error, empirical equations were developed for FT in terms of TT and SHBG. RESULTS: Comparison between the empirical FT equations with the laboratory FT measurements as well as three widely used calculated FT methods showed the empirical FT formulae had superior fidelity with laboratory measurements while previous FT formulae overestimated and deviated systematically from the laboratory FT values. CONCLUSION: We conclude that these simple, assumption-free empirical FT equations can estimate accurately blood FT from TT and SHBG measured in the same samples with the present assay methods and have suitable properties for wider application to evaluate the clinical utility of blood FT measurements.

Adult↗
PubMed2005

Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men.

OBJECTIVE: Androgen deficiency (AD) leads to bone loss and contributes to osteoporotic fractures in men. Although low bone mineral density (BMD) in AD men is improved by testosterone replacement, the responses vary between individuals but the determinants of this variability are not well defined. DESIGN AND METHODS: Retrospective review of dual energy X-ray absorptiometry (DEXA) of the lumbar spine and proximal femur in men with established AD requiring regular androgen replacement therapy (ART). After a DEXA scan all men were treated with testosterone implants (800 mg, approximately 6 month intervals). Patients were classified as having a congenital, childhood, or post-pubertal onset, as well as according to the adequacy of treatment prior to their first DEXA scan as untreated, partially treated or well treated. RESULTS: Men with AD requiring regular ART (n = 169, aged 46.3+/-1.1 years, range 22-84 years) underwent a DEXA scan prior to being treated with testosterone implants (800 mg, approximately 6 month intervals). In cross-sectional analysis at the time of the first DEXA scan untreated men (n = 24) had significantly reduced age-adjusted BMD at all four sites (L1-L4, femoral neck, Ward's triangle and trochanter). Well-treated men (n = 77) had significantly better age-adjusted BMD at all four sites compared with those who were partially treated (n = 66) or untreated (n = 24) with their age-adjusted BMD being normalized. In a longitudinal assessment of men (n = 60) who had two or more serial DEXA scans, at the second DEXA scan after a median of 3 years, men who were previously partially treated (n = 19) or untreated (n = 11) had proportionately greater improvements in BMD, significantly for Ward's triangle (P = 0.025) and the trochanter (P = 0.044) compared with men (n = 30) previously well treated. CONCLUSIONS: The present study demonstrates a positive relationship between adequacy of testosterone replacement and BMD in men with overt organic AD. Additionally, the BMD of well-treated AD men approximates that of age-matched non-AD controls. The greatest BMD gains are made by those who have been either untreated or partially treated, and optimal treatment over time (median 3 years) normalizes BMD to the level expected for healthy men of the same age.

Absorptiometry, Photon↗
PubMed2004

Trends and regional differences in testosterone prescribing in Australia, 1991-2001.

OBJECTIVES: To analyse temporal trends and geographical variations in testosterone prescribing in Australia. DESIGN AND SETTING: An analysis of testosterone prescribing over the past 11 years according to products and region, determined by Pharmaceutical Benefits Scheme (PBS) expenditure in Australian states and territories. MAIN OUTCOME MEASURE: Patterns of monthly PBS expenditure on injectable, oral and implantable testosterone products from 1 January 1991 to 30 December 2001, classified by state or territory. RESULTS: There were two periods (1993-1994 and 1998-1999) of striking upsurge followed by declines in national total prescribing of testosterone. These changes were more prominent for oral than injectable testosterone products, and patterns were similar in all regions, apart from a disproportionately higher peak in Western Australia in 1998. On a per-capita basis, Western Australia showed a dramatic increase in prescribing of oral and implantable, but not injectable, testosterone coinciding with the opening of a franchised men's sexual health clinic in Perth. CONCLUSION: The two striking upsurges in testosterone prescribing despite no convincing new evidence to justify them appear to reflect promotional activity to prescribe testosterone for older men, rather than overcoming the underdiagnosis of androgen deficiency related to pituitary or testicular disease in younger men. The curtailments after the introduced restrictions to PBS prescribing for older men without overt androgen deficiency were partial and temporary, suggesting that such regulatory barriers are only partly successful in counteracting the commercial and populist pressure driving excessive testosterone prescribing. Professional and community education is needed for appropriate diagnosis of genuine androgen deficiency in younger men, while discouraging unproven testosterone treatment for ageing men.

Australia↗
PubMed2004

Designer androgens in sport: when too much is never enough.

The recent identification of tetrahydrogestrinone (THG), the first true "designer androgen," as a sports doping agent reflects both an alarmingly sophisticated illicit manufacturing facility and an underground network of androgen abusers in elite sports, as well as the still untapped potential for designer androgens in medicine. Never marketed, THG was apparently developed as a potent androgen that was undetectable by conventional International Olympic Committee-mandated urinary sports doping tests. As a potent androgen and progestin with unspecified contaminants, its distribution for use at high doses without any prior biological or toxicological evaluation poses significant health risks. Yet this diversion of science also highlights the prospect of designer androgens for use in human medicine. Designer androgens also offer the possibility of tissue-specific effects enhancing the beneficial effects of androgens while mitigating the undesirable ones. Further developments require better understanding of the postreceptor tissue selectivity of androgens, comparable to the mechanism underlying that of partial estrogen agonists (SERMs). This experience highlights the ongoing need for vigilance to detect novel drug doping strategies in order to maintain fairness and safety in elite sports. This will require the deployment of generic catch-all tests, such as sensitive and specific in vitro androgen bioassays, coupled with the development of mass spectrometry-based tests for specific doping agents.

Androgens↗
PubMed2004

Effects of medroxyprogesterone and estradiol on the recovery of spermatogenesis in irradiated rats.

Suppression of intratesticular testosterone (ITT) levels is required for spermatogenic recovery in rats after irradiation, but maintenance of peripheral testosterone (T) levels is important for many male functions. Considering the preservation of peripheral T while suppressing ITT, we tested the effects of a combination of a progestin, medroxyprogesterone acetate (MPA), plus T on spermatogenic recovery after irradiation, and compared its effects to those of T alone or T combined with estradiol (E2). Rats were given testicular irradiation (6 Gy) and treated during wk 3-7 after irradiation with MPA + T, or the individual steroids with or without GnRH antagonist (GnRH-ant), or GnRH-ant alone, or T + E2. Whereas GnRH-ant alone stimulated differentiation in 55% of tubules 13 wk after irradiation compared with 0% in irradiated-only rats, the addition of MPA reduced the percentage of tubules showing differentiation to 18%. However, T or MPA alone or the combination of the two induced germ cell differentiation in only 2-4% of tubules. In contrast, E2 stimulated differentiation in 88% of tubules, and T combined with E2 still resulted in differentiation in 30% of tubules. Although both MPA and E2 suppressed ITT levels to approximately 2% of control (2 ng/g testis), MPA was a less effective stimulator of spermatogenic recovery than E2 or GnRH-ant alone. MPA's function as a weak androgen was likely responsible for inhibiting spermatogenic recovery, as was the case for all other tested androgens. Thus, for clinical protection or restoration of spermatogenesis after radiation or chemotherapy by suppressing T production, MPA, at least in the doses used in the present study, is suboptimal. The combination of an estrogen with T appears to be most effective for stimulating such recovery.

Animals↗
PubMed2004

11: Androgen deficiency and replacement therapy in men.

Androgen deficiency is a clinical diagnosis confirmed by hormone assays. Among younger men, androgen deficiency is usually due to underlying hypothalamopituitary or testicular disorders. Androgen replacement therapy should be started after proof of androgen deficiency and should continue lifelong with monitoring. Men presenting with erectile dysfunction should be evaluated for androgen deficiency, but it is an uncommon cause; if overt androgen deficiency is confirmed, an underlying disorder needs further specialist investigation. In the absence of characteristic underlying testicular or pituitary disorders, new diagnosis of androgen deficiency in older men is difficult because of the non-specific symptoms and the decline in blood testosterone levels seen in healthy ageing and chronic medical disorders. There remains no convincing evidence that androgen therapy is either effective treatment or safe for older men unless they have frank androgen deficiency.

Adolescent↗
PubMed2004

Complete Sertoli cell proliferation induced by follicle-stimulating hormone (FSH) independently of luteinizing hormone activity: evidence from genetic models of isolated FSH action.

Defining the gonadal effects of FSH distinct from those of LH remains difficult. We have characterized and compared the level of Sertoli and germ cell development in three mouse models recently created to isolate FSH activity from LH effects. Two models used LH-deficient hypogonadal (hpg) mice to selectively study either pituitary-independent transgenic (tg) FSH or ligand-independent activated tg FSH receptor (FSHR(+)) expression, and the third model used LH receptor (LHR)-deficient mice to isolate and examine endogenous mouse FSH effects. Stereological evaluation revealed tg-FSH or tg-FSHR(+) activity significantly increased total Sertoli cell numbers per testis in both hpg models relative to control hpg testes. Furthermore, tg-FSH dose-dependently restored hpg Sertoli cells to wild-type (wt) (non-hpg) levels, and LHR-/- testes also exhibited wt Sertoli numbers. Spermatogonial proliferation and meiotic development were enhanced by tg-FSHR(+) or tg-FSH. Despite producing normal Sertoli numbers, isolated tg-FSH activity only increased total spermatogonia and spermatocyte populations to 57 and 44% of wt, which was comparable to spermatogonia and spermatocyte numbers observed in LHR-null testes (45 and 34% of wt). Selective FSH activity initiated round spermatid formation in all three models. However, elongated spermatid formation was detected in tg-FSH and tg-FSHR(+) hpg testes but not in LHR-/- testes, which may reflect even lower intratesticular testosterone levels in LHR-null compared with hpg testes. FSH increased round and elongated spermatid numbers in hpg testes to 16 and 6% of wt without altering intratesticular testosterone levels, but failed to produce spermatozoa demonstrating the inability of FSH to complete spermatogenesis. These findings revealed that full Sertoli cell proliferation can be accomplished by FSH activity without LH requirement, and although postnatal mitotic and meiotic germ cell development can be promoted by FSH alone, LH-mediated effects remain a critical determinant for initiating the full complement of germ cells and final stages of postmeiotic development.

Animals↗
PubMed2004

Recombinant human chorionic gonadotropin but not dihydrotestosterone alone stimulates osteoblastic collagen synthesis in older men with partial age-related androgen deficiency.

Several randomized trials of androgen supplementation in older men have been undertaken. However, the relative contributions of testosterone (T) and estrogens on bone metabolism in aging men are controversial. Within the setting of two double-blind, placebo-controlled studies, we evaluated the effect of dihydrotestosterone (DHT) and recombinant human chorionic gonadotropin (rhCG) on bone turnover in healthy, community-dwelling older men with partial androgen deficiency (total T < or = 15 nmol/liter). In the first study, 35 men (age 68.3 +/- 6.8 yr; baseline T, 13.9 +/- 3.3 nmol/liter) were randomized to receive either daily transdermal DHT (n = 17) or placebo for 3 months. In the second study, 40 men (age 67.4 +/- 5.4 yr; baseline T, 11.4 +/- 2.2 nmol/liter) were randomized to receive either rhCG s.c. (n = 20), two injections weekly, or placebo for 3 months. The following parameters were measured before, monthly during, and 1 month after treatment: serum T, estradiol (E2), and LH; markers of bone formation, serum amino-terminal propeptide of type I procollagen (S-PINP) and osteocalcin; markers of bone resorption, serum carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline. Compared with placebo, treatment with DHT significantly increased serum DHT and suppressed LH and T levels, whereas E2 concentrations and markers of bone turnover did not change. In contrast, rhCG therapy significantly increased both T and E2, with the increases in E2 being supraphysiological. At the same time, rhCG significantly increased S-PINP concentrations with peak levels after 1 month (Delta40%; P = 0.02 compared with placebo). In contrast, serum osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline levels did not change. The change in S-PINP levels correlated with the change in E2 levels (r = 0.59; P = 0.02) but not with a change in T. We conclude that in older men with partial age-related androgen deficiency, rhCG treatment stimulates osteoblastic collagen formation proportionally to increased E2 concentrations but does not alter markers of mature osteoblastic function or bone resorption. In contrast, treatment with a pure, nonaromatizable androgen (DHT) has no effect on bone turnover despite a 20-fold increase in serum levels. Bone resorption was not accelerated during unchanged (DHT) or increased (rhCG) E2 levels, suggesting that minimal E2 levels are needed to maintain stable resorption, although direct androgen receptor-mediated effects cannot be excluded. If androgen supplementation is required for aging men, aromatizable androgens with sufficient endogenous estrogenic activity may have the most beneficial effects on bone.

Aged↗
PubMed2004

Tetrahydrogestrinone is a potent androgen and progestin.

Tetrahydrogestrinone (THG) was recently identified as a novel steroid used illicitly to improve athletic performance. Although its structure is closely related to gestrinone, a 19-nor progestin, and resembles that of trenbolone, THG was never marketed, so information on its hormonal properties is not known. In this study, we demonstrate that THG is a highly potent androgen and progestin in a yeast-based in vitro bioassay system expressing human androgen and progesterone receptors. It has no estrogenic activity and no antagonism for any of the three steroid receptor classes.

Androgens↗
PubMed2003

Dihydrotestosterone promotes vascular cell adhesion molecule-1 expression in male human endothelial cells via a nuclear factor-kappaB-dependent pathway.

There exists a striking gender difference in atherosclerotic vascular disease. For decades, estrogen was considered atheroprotective; however, an alternative is that androgen exposure in early life may predispose men to earlier atherosclerosis. We recently demonstrated that the potent androgen, dihydrotestosterone (DHT), enhanced the binding of monocytes to the endothelium, a key early event in atherosclerosis, via increased expression of vascular cell adhesion molecule-1 (VCAM-1). We now show that DHT mediates its effects on VCAM-1 expression at the promoter level through a novel androgen receptor (AR)/nuclear factor-kappaB (NF-kappaB) mechanism. Human umbilical vein endothelial cells were exposed to 4-400 nm DHT. DHT increased VCAM-1 mRNA in a dose- and time-dependent manner. The DHT effect could be blocked by the AR antagonist, hydroxyflutamide. DHT increased VCAM-1 promoter activity via NF-kappaB activation without affecting VCAM-1 mRNA stability. Using 5' deletion analysis, it was determined that the NF-kappaB sites within the VCAM-1 promoter region were responsible for the DHT-mediated increase in VCAM-1 expression; however, coimmunoprecipitation studies suggested there is no direct interaction between AR and NF-kappaB. Instead, DHT treatment decreased the level of the NF-kappaB inhibitory protein. DHT did not affect VCAM-1 protein expression and monocyte adhesion when female endothelial cells were tested. AR expression was higher in male, relative to female, endothelial cells, associated with increased VCAM-1 levels. These findings highlight a novel AR/NF-kappaB mediated mechanism for VCAM-1 expression and monocyte adhesion operating in male endothelial cells that may represent an important unrecognized mechanism for the male predisposition to atherosclerosis.

Adult↗
PubMed2003

Dehydroepiandrosterone, an adrenal androgen, increases human foam cell formation: a potentially pro-atherogenic effect.

OBJECTIVES: We studied the effects of dehydroepiandrosterone (DHEA), an abundant adrenal androgen on two key early events of atherogenenis: 1) human monocyte adhesion to vascular endothelium, and 2) human foam cell formation. BACKGROUND: In the U.S., where DHEA is available without prescription, there has recently been a rapid increase in unsupervised self-administration of DHEA. The vascular biologic effects of DHEA are largely unknown, however. METHODS: Regarding adhesion, human umbilical vein endothelial cells (HUVECs), exposed to either DHEA (42 or 420 nmol/l) or control, were incubated with human monocytes, and adhesion was measured by hemocytometry. Surface expression of endothelial cell adhesion molecules was measured by ELISA. Regarding foam cell formation, studies of lipid loading were performed on macrophages treated with DHEA or control and/or the androgen receptor antagonist hydroxyflutamide (HF) (4 micromol/l). Intracellular cholesterol and cholesteryl esters (CE) were quantified by high-performance liquid chromatography. Expression of foam cell formation-related genes was measured by reverse-transcription polymerase chain reaction. RESULTS: DHEA produced a dose-dependent receptor-mediated increase in the male macrophage CE content (up to 120 +/- 4% of control values, p = 0.015). DHEA upregulated messenger ribonucleic acid expression of the lipoprotein-processing enzymes acyl coenzyme A:cholesterol acyltransferase I and lysosomal acid lipase by 3.4- and 5.3-fold, respectively (p < 0.05 vs. control), but had no effect on scavenger receptor expression (p > 0.2). There was no significant effect of DHEA on monocyte-endothelial adhesion (<10% change in values, p = 0.56) or endothelial cell expression of cell adhesion molecules (p > 0.1). CONCLUSIONS: DHEA increases human macrophage foam cell formation, a potentially pro-atherogenic effect. This effect appears to be mediated via the androgen receptor and involves the upregulation of lipoprotein-processing enzymes.

Acyl Coenzyme A↗
PubMed2003

Androgens up-regulate atherosclerosis-related genes in macrophages from males but not females: molecular insights into gender differences in atherosclerosis.

OBJECTIVES: This study investigated the effects of androgens on gene expression in male- and female-donor macrophages. BACKGROUND: Men have more severe coronary disease than women. Androgen exposure increases foam cell formation in male but not female macrophages, and male macrophages express >4-fold more androgen receptor messenger ribonucleic acid than female macrophages. Therefore, androgen exposure may have gender-specific and potentially pro-atherogenic effects in macrophages. METHODS: Utilizing complementary deoxyribonucleic acid arrays, we studied the effects of a pure androgen (dihydrotestosterone, 40 nmol/l) on human monocyte-derived macrophages from healthy male and female donors (n = 4 hybridizations; 2 men, 2 women). Differential expression of atherosclerosis-related genes was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) in five male and five female donors. Functional corroboration of foam cell formation-related findings was undertaken by experiments using (125)I-acetylated low-density lipoprotein (AcLDL). RESULTS: In male macrophages, androgen treatment produced differential up-regulation of 27 genes concentrated in five functional classes: 1) lipoprotein processing; 2) cell-surface adhesion; 3) extracellular signaling; 4) coagulation and fibrinolysis; and 5) transport protein genes. By contrast, none of 588 genes were up-regulated in female macrophages. By RT-PCR, we confirmed the gender-specific up-regulation of six of these atherosclerosis-related genes: acyl coenzyme A:cholesterol acyl transferase I, lysosomal acid lipase (LAL), caveolin-2, CD40, vascular endothelial growth factor-165 receptor, and tissue factor pathway inhibitor. Functionally, androgen-treated male macrophages showed increased rates of lysosomal AcLDL degradation, by 45% to 75% after 15 to 20 h of (125)I-AcLDL incubation (p = 0.001), consistent with increased LAL activity. CONCLUSIONS: Androgens increase expression of atherosclerosis-related genes in male but not female macrophages, with functional consequences. These findings may contribute to the male predisposition to atherosclerosis.

Adult↗