Acute Supplementation with High Dose Vitamin D3 Increases Serum Anti-Müllerian Hormone in Young Women.

Anti-Müllerian hormone (AMH) is a paracrine regulator of ovarian follicles. Vitamin D (Vit D) regulates AMH production in vitro, but its role as a regulator of ovarian AMH production is contentious. If Vit D influences ovarian AMH production, then an acute rise in Vit D level should lead to an acute rise in circulating AMH levels. This hypothesis was tested with a randomized double-blind design, with 18-25-year-old women recruited from the community. The study was conducted in early spring, when the marker of Vit D level (25-hydroxyvitamin D, 25(OH)D) tends to be at its nadir. The women consumed either an oral dose of 50,000 IU of Vit D3 (n = 27) or placebo (n = 22). The initial 25(OH)D ± SD value was 53.6 ± 23.3 nmol/L, with 42 of the 49 women having a value below 75 nmol/L, consistent with seasonal nadir. All women receiving Vit D3 treatment exhibited a robust increase in serum 25(OH)D within 1 day (15.8 ± 1.1 nmol/L (n = 27), p < 0.0001), with the increase sustained over the study week. Circulating levels of AMH in the women receiving Vit D3 progressively rose during the following week, with a mean increase of 12.9 ± 3.7% (n = 24, p = 0.001). The study supports the hypothesis that Vit D's positive effects on the fertility of woman may involve the regulation of ovarian AMH levels.

Serum anti-Mullerian hormone (AMH) levels correlate with infrarenal aortic diameter in healthy older men: is AMH a cardiovascular hormone?

Anti-Müllerian hormone (AMH) is a gonadal hormone present in the blood in men and pre-menopausal women. AMH regulates male sexual differentiation but has no putative function in adulthood. In recent studies, high AMH levels are associated with absence of cardiovascular disease in men and smaller atherosclerotic burden in monkeys. Mechanistically, AMH has downstream convergence with known regulators of the cardiovascular system, while the specific receptor for AMH is present in murine aorta and the human heart. Our primary objective was to examine whether AMH levels in healthy men correlated with the physical characteristics of their aorta. Our secondary aim was to document whether men with distinct vascular disorders expressed different levels of AMH. Serum AMH assayed by ELISA in 153 men (54-93 years) free from vascular disease inversely correlated with the ultrasonographic diameters of the distal- (r=-0.22, P=0.006) and mid-infrarenal aorta (r=-0.26, P=0.008). This association was similar in magnitude but opposite to that of body surface area (largest known determinant of aortic diameter) and independent of known cardiovascular risk factors. This relationship is specific to AMH, as inhibin B, a Sertoli cell hormone-like AMH, did not correlate with aortic diameter (r=-0.04, P=0.66) despite partially correlating with AMH. Among men with known vascular disease, higher AMH levels were associated with varicose vein disease, while men with higher levels of AMH were under-represented in the abdominal aortic aneurysm relative to the healthy cohort. These findings identify AMH as a novel putative regulator of the cardiovascular system.

Elderly men have low levels of anti-Müllerian hormone and inhibin B, but with high interpersonal variation: a cross-sectional study of the sertoli cell hormones in 615 community-dwelling men.

The Sertoli cells of the testes secrete anti-Müllerian hormone (Müllerian inhibiting Substance, AMH) and inhibin B (InhB). AMH triggers the degeneration of the uterine precursor in male embryos, whereas InhB is part of the gonadal-pituitary axis for the regulation of sperm production in adults. However, both hormones are also putative regulators of homeostasis, and age-related changes in these hormones may therefore be important to the health status of elderly men. The levels of AMH in elderly men are unknown, with limited information being available about age-related changes in InhB. We have therefore used ELISAs to measure Sertoli cell hormone levels in 3 cohorts of community-dwelling men in New Zealand. In total, 615 men were examined, 493 of which were aged 65 or older. Serum AMH and InhB levels inversely correlated with age in men older than 50 years (p<0.001) but not in the younger men. A minority of elderly men had undetectable levels of AMH and InhB. The variation in hormone levels between similarly aged men increased with the age of men. AMH and InhB partially correlated with each other as expected (r = 0.48, p<0.001). However, the ratio of the two Sertoli hormones varied significantly between men, with this variation increasing with age. Elderly men selected for the absence of cardiovascular disease had AMH levels similar to those of young men whereas their InhB levels did not differ from aged-matched controls. These data suggests that Sertoli cell number and function changes with age, but with the extent and nature of the changes varying between men.

The level of serum anti-Müllerian hormone correlates with vitamin D status in men and women but not in boys.

CONTEXT: Anti-Müllerian hormone (AMH) is a gonad-specific hormone, which is extensively used as a marker of gonadal status. The level of serum AMH has a high variance in similar individuals for reasons that are unknown. The AMH gene promoter contains a vitamin D response element that may cause vitamin D status to influence serum AMH levels. AIM: The objective of the study was to determine whether serum levels of AMH are related to 25-hydroxyitamin D [25(OH)D)] status. SETTING: This was a correlative and intervention study. PARTICIPANTS: Three cohorts of participants were analyzed; mature men (n = 113), premenopausal women (n = 33), and 5- to 6-yr-old boys (n = 74). Women were given a daily supplement of ergocalciferol, cholecalciferol, or a placebo for 6 months and provided baseline and posttreatment blood samples. MAIN OUTCOME MEASURES: Serum AMH and 25(OH)D were measured and analyzed for covariation. RESULTS: Serum AMH positively correlated with 25(OH)D in men (r = 0.22, P = 0.02) but not boys. Both 25(OH)D and AMH levels exhibited seasonal variation in women, with an 18% decrease in AMH levels in winter compared with summer (P = 0.01). Change in AMH level correlated with the initial AMH level and the magnitude of change in vitamin D levels (r = 0.36, P = 0.004). Cholecalciferol supplementation prevented seasonal AMH change. CONCLUSION: Vitamin D may be a positive regulator of AMH production in adults, and vitamin D deficiency may confound clinical decisions based on AMH. Vitamin D deficiency should be considered when serum AMH levels are obtained for diagnosis.

The stature of boys is inversely correlated to the levels of their sertoli cell hormones: do the testes restrain the maturation of boys?

The testes of preadolescent boys appear to be dormant, as they produce only trace levels of testosterone. However, they release supra-adult levels of Müllerian Inhibiting Substance (MIS, anti-Müllerian hormone) and lesser levels of inhibin B (InhB), for unknown reasons. Boys have a variable rate of maturation, which on average is slower than girls. The height of children relative to their parents is an index of their maturity. We report here that a boy's level of MIS and InhB is stable over time and negatively correlates with his height and his height relative to his parent's height. This suggests that boy's with high levels of MIS and InhB are short because they are immature, rather than because they are destined to be short men. The levels of MIS and InhB in the boys did not correlate with known hormonal modulators of growth, and were additive with age and the growth hormone/IGF1 axis as predictors of a boy's height. If MIS and InhB were causal regulators of maturity, then the inter-boy differences in the levels of these hormone produces variation in maturation equivalent to 18-months of development. MIS and InhB may thus account for most of the variation in the rate of male development. If boys lacked these hormones, then an average 5-year-old boy would be over 5 cm taller than age-matched girls, making boys almost as dimorphic as men, for height. This indicates that boys have a high growth potential that is initially suppressed by their testes. The concept of the childhood testes suppressing an adult male feature appears paradoxical. However, the growth of children requires intergenerational transfer of nutrients. Consequently, the MIS/InhB slowing of male growth may have been historically advantageous, as it would minimizes any sex bias in the maternal cost of early child rearing.