A cohort effect on serum testosterone levels in Finnish men

Perheentupa, Antti; Mäkinen, Juuso; Laatikainen, Tiina; Vierula, Matti; Skakkebæk, Niels E.; Andersson, Anna‐Maria; Toppari, Jorma

doi:10.1530/eje-12-0288

Cited by 52 publications

(32 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is also evidence of an increase in the number of boys with congenital abnormalities of the genitalia [59,60,61,62]. Finally, investigators from the USA and Europe have reported lower serum testosterone levels among normal men [63,64,65]. …”

Section: Perspectives and Conclusionmentioning

confidence: 99%

A Brief Review of the Link between Environment and Male Reproductive Health: Lessons from Studies of Testicular Germ Cell Cancer

Skakkebæk

2016

Horm Res Paediatr

View full text Add to dashboard Cite

During the past few decades there has been a significantly increasing trend in germ cell tumours all over the world, particularly in countries with Caucasian populations. The changes in incidence have occurred so fast that only environmental factors can explain this development. This review focuses on the hypothesis that testicular germ cell cancer, which originates from germ cell neoplasia in situ, is of foetal origin and associated with other male reproductive problems through a testicular dysgenesis syndrome, also including foetal origin of impaired spermatogenesis, hypospadias and cryptorchidism. There is little doubt that environmental factors associated with modern lifestyles have - in a broad sense - had an adverse influence on male reproductive health. The hypothesis that exposure to endocrine-disrupting chemicals plays a fundamental role in this trend is plausible. This is based on evidence from animal studies that demonstrate adverse reproductive effects caused by a number of endocrine-disrupting chemicals to which humans are exposed as part of our modern lifestyle.

show abstract

Section: Perspectives and Conclusionmentioning

confidence: 99%

A Brief Review of the Link between Environment and Male Reproductive Health: Lessons from Studies of Testicular Germ Cell Cancer

Skakkebæk

2016

Horm Res Paediatr

View full text Add to dashboard Cite

show abstract

“…Cross-sectional studies have associated low testosterone levels with increased cardiovascular risk factors (diabetes mellitus, the metabolic syndrome, abnormal lipid profile) and increased cardiovascular risk in men. 2–5 This is particularly important given the progressive population-level decline in serum testosterone concentrations in men from developed countries 6–8 which has resulted in a dramatic increase in the use of androgen replacement therapy (ART). Indeed, there has been a 10-fold increase in prescribed ART in the USA 9 and nearly a 3-fold increase in the UK 10 in the past decade.…”

Section: Introductionmentioning

confidence: 99%

Modulation of neointimal lesion formation by endogenous androgens is independent of vascular androgen receptor

Hadoke

Mair

et al. 2014

Cardiovascular Research

View full text Add to dashboard Cite

AimsLow androgen levels have been linked with an increased risk of cardiovascular disease in men. Previous studies have suggested that androgens directly inhibit atherosclerotic lesion formation although the underlying mechanisms for this remain unclear. This study addressed the hypothesis that endogenous androgens inhibit arterial remodelling by a direct action on the androgen receptor (AR) in the vascular wall.Methods and resultsWe studied a series of novel mouse lines with cell-specific deletion of the AR in either the endothelium or in smooth muscle cells or both cell types. Findings were compared with a model of global androgen deficiency in wild-type mice (castrated). We characterized the cardiovascular phenotype, vascular pharmacology and histology, and assessed neointimal lesion formation following vascular injury to the femoral artery. Cell-specific AR deletion did not alter body weight, circulating testosterone levels or seminal vesicle weight, but caused limited alterations in arterial contractility and blood pressure. Neointimal lesion formation was unaltered by selective deletion of AR from the vascular endothelium, smooth muscle, or both cell types. Castration in wild-type mice increased neointimal lesion volume (Sham vs. Castration: 2.4 × 107 ± 4.5 × 106 vs. 3.9 × 107 ± 4.9 × 106 µm3, P = 0.04, n = 9–10).ConclusionVascular cell-specific AR deletion had no effect on neointimal lesion formation, while low systemic androgen levels adversely affect neointimal lesion size. These findings suggest that the cardio-protective effects of androgens are mediated either by AR outside the vasculature or by AR-independent mechanisms.

show abstract

“…Such fetal programming applies to common disorders encapsulated in the metabolic syndrome (2), which are interlinked in adult men with low testosterone levels (3). Large studies from the United States (4) and Europe (5,6) also show that testosterone levels in men of all ages are declining with later year of birth. Aging is itself associated with declining testosterone levels and a high incidence of primary/compensated hypogonadism (7)(8)(9).…”

mentioning

confidence: 99%

Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells

Kilcoyne

Smith

Atanassova

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

160

135

View full text Add to dashboard Cite

Fetal growth plays a role in programming of adult cardiometabolic disorders, which in men, are associated with lowered testosterone levels. Fetal growth and fetal androgen exposure can also predetermine testosterone levels in men, although how is unknown, because the adult Leydig cells (ALCs) that produce testosterone do not differentiate until puberty. To explain this conundrum, we hypothesized that stem cells for ALCs must be present in the fetal testis and might be susceptible to programming by fetal androgen exposure during masculinization. To address this hypothesis, we used ALC ablation/regeneration to identify that, in rats, ALCs derive from stem/progenitor cells that express chicken ovalbumin upstream promoter transcription factor II. These stem cells are abundant in the fetal testis of humans and rodents, and lineage tracing in mice shows that they develop into ALCs. The stem cells also express androgen receptors (ARs). Reduction in fetal androgen action through AR KO in mice or dibutyl phthalate (DBP) -induced reduction in intratesticular testosterone in rats reduced ALC stem cell number by ∼40% at birth to adulthood and induced compensated ALC failure (low/normal testosterone and elevated luteinizing hormone). In DBP-exposed males, this failure was probably explained by reduced testicular steroidogenic acute regulatory protein expression, which is associated with increased histone methylation (H3K27me3) in the proximal promoter. Accordingly, ALCs and ALC stem cells immunoexpressed increased H3K27me3, a change that was also evident in ALC stem cells in fetal testes. These studies highlight how a key component of male reproductive development can fundamentally reprogram adult hormone production (through an epigenetic change), which might affect lifetime disease risk.adult Leydig stem/progenitor cells | compensated Leydig cell failure | GATA4 | ethane dimethane sulfonate

show abstract

A cohort effect on serum testosterone levels in Finnish men

Cited by 52 publications

References 22 publications

A Brief Review of the Link between Environment and Male Reproductive Health: Lessons from Studies of Testicular Germ Cell Cancer

A Brief Review of the Link between Environment and Male Reproductive Health: Lessons from Studies of Testicular Germ Cell Cancer

Modulation of neointimal lesion formation by endogenous androgens is independent of vascular androgen receptor

Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells

Contact Info

Product

Resources

About