Endocrine Abstracts

We found that mast cells were present in pubertal mammary glands, and hypothesized that they participate in mammary morphogenesis and are sensitive to IGF1, which is essential for mammary development.

As independently reported in another model of mast cell deficiency (Developmental Biology 2010 337 124), mast cell-deficient W/W^v mice had significantly less terminal end buds and ducts and smaller gland areas than controls at 3, 6, and 9 weeks of age (P<0.01).

In 75-day-old oophorectomized Ames dwarf mice (deficient in GH, PRL, and TSH) IGF1+E₂ for 5 days significantly increased the number of tryptase-positive periglandular and stromal mast cells as compared with vehicle (P<0.01 and <0.02 respectively). Mast cell increase coincided with mammary development. Mammary mast cell dependence on IGF1 was confirmed by treatment with pasireotide, which blocks IGF1 action in the mammary gland probably by inducing IGF1 binding protein 5. Pasireotide for 7 days reduced periglandular and stromal mast cell density in 28-day-old intact CD rats (P<0.02 and <0.05 respectively), and prevented GH + E₂ from increasing mammary mast cell number in hypophysectomized, oophorectomized 28-day-old CD rats (P<0.02).

To determine whether IGF1 also had an effect on mast cells elsewhere in the body, we cultured bone marrow-derived mast cells from C57Bl/6 mice. Formazan-producing viable mast cells were significantly increased in number in response to 100 ng/ml IGF1 added to serum-free culture medium during prolonged serum starvation (P<0.05 after 24 h and <0.01 after 48 h). IGF1 effect was associated with activation of the anti-apoptotic AKT/PKB pathway. PQ401, an IGF1 receptor phosphorylation inhibitor, blocked AKT activation and prevented IGF1 from rescuing serum-starved mast cells, while somatostatin-14 had no effect.

Our results support that mast cells are involved in mammary development. They further suggest that growth of mammary mast cell may depend, in part, on IGF1.