Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is a disorder associated with infertility and metabolic disturbances. Ovaries of PCOS women contain an increased number of growing follicles. Such an ovarian phenotype is also observed in mice lacking the ovary-specific growth factor anti-Müllerian hormone (AMH). To determine the interaction between ovarian and metabolic function, we studied the metabolic phenotype of mice lacking AMH signaling as a model for an altered profile in ovarian growth factors.

Female mice lacking AMH (AMHKO) or its specific type 2 receptor (MRKI) and WT littermates (WT) were analyzed at 4, 5 and 8 months of age. Body weight, white and brown adipose tissue (WAT and BAT) weight, and serum adipokine levels were measured, and an intraperitoneal glucose tolerance test (IPGTT) was performed.

Body weight did not differ between genotypes. Similarly, glucose tolerance did not differ at 4 months. However, at 5 months of age, AMHKO and MRKI mice had a better glucose tolerance than WT mice (P=0.002), who displayed a worsening in glucose tolerance with increasing age. At 5 months, WAT depots of AMHKO and MRKI mice weighed 10–40% less and contained smaller adipocytes (P<0.001). In agreement, leptin levels were 40–80% reduced in AMHKO and MRKI mice compared to WT mice. Interestingly, AMHKO and MRKI mice had more active BAT and displayed increased browning of WAT, illustrated by increased UCP1 staining in WAT compared to WT mice. At 8 months, AMHKO mice continued to have smaller adipocytes (P<0.001), lower leptin levels (P<0.05), and tended to have improved glucose tolerance (P<0.07) combined with lower insulin levels (P<0.05) compared to WT mice.

In conclusion, in the absence of AMH signaling mice are protected against the age-related worsening in metabolism. This suggests that an altered profile in ovarian growth factors may affect metabolism and may modulate the effect of metabolic aging.