Is Anti-Müllerian Hormone a Hormone?
Dennis, Nicola Amy
The aim of this thesis is to investigate if Anti-Müllerian hormone (AMH) is a hormone. AMH is a protein produced in the testes and ovaries. The classical function of AMH is to regulate Müllerian duct regression in the male fetus. However, AMH continues to be expressed in males after this time for unknown reasons. AMH is present at very high levels in the blood of males during infancy and childhood. After puberty, AMH levels are present at lower levels in men. Furthermore, AMH is also present in women from puberty until menopause. It is not known why AMH is secreted into the bloodstream or why its levels are variable throughout development. Therefore, despite its name it is not known if AMH is a hormone. To earn this classification an endocrine function for AMH must be identified. That is, circulating AMH must be shown to interact with receptors in cells outside the gonads to induce an effect of some kind. A preliminary screen of the AMH type II receptor (AMHRII) expressing tissues was performed with an AMHRII reporter mouse. This analysis suggested that AMHRII expression is extensive in the fetus including cells of the cardiovascular, skeletal, respiratory, digestive, nervous and integumentary systems. While analysis in the adult AMHRII reporter mouse suggested AMHRII expression was found in the cardiovascular system and cartilage. Findings from a correlative study comparing AMH levels and cardiovascular measures in healthy men indicated that AMH levels inversely correlate with aortic diameter independent of other known determinants for this measure. This suggests that AMH may be a regulator of blood vessel size. Consistent with this AMH levels were significantly altered in abdominal aortic aneurysms and varicose veins which are both conditions of pathological blood vessel enlargement. Correlative studies in healthy school boys showed that AMH levels inversely correlated with height and the proportion of adult growth the boys had achieved. This indicates that AMH may be a hormonal regulator of bone maturation. However, Inhibin B also correlated with boy height measures which confounded interpretation of the results. Animal studies showed that adult AMH-/- mice of both sexes had significantly shorter bones than their wildtype littermates. This is consistent with AMH having a direct action on bone, although the growth and bone measurements were not altered in young AMH-/- mice which indicates this association is complex. Further human studies, found that AMH levels correlate with vitamin D levels in men and women. Additionally, AMH levels and vitamin D levels were both shown to decrease in winter with vitamin D supplementation sufficient to prevent the winter decline in AMH levels. This indicates that AMH levels are regulated by vitamin D through a previously characterised vitamin D element in the AMH gene. This thesis, presents the first evidence that AMH has putative hormonal functions in humans and that AMH concentration in the blood is regulated. This suggests that AMH found in the blood is not simply leakage from the gonads but that AMH is secreted to perform endocrine signalling.
Advisor: McLennan, Ian
Degree Name: Doctor of Philosophy
Degree Discipline: Anatomy
Publisher: University of Otago
Keywords: Anti-Müllerian hormone; Müllerian inhibing substance; Transforming growth factor beta superfamily; Inhibin; Vitamin D; Child growth; Aortic diameter
Research Type: Thesis