Morphological and histological studies in mammary glands of GH-overexpressing transgenic mice.

Mariana A. Bojorge¹, Johanna G. Miquet¹, Silvia Vanzulli², Carolina A. Lamb³, Lorena González¹

Growth Hormone (GH) is central to stimulate growth, development and metabolism. It plays crucial roles in mammary gland development and growth, and its upregulation has been associated with breast cancer promotion and/or progression. To ascertain how high GH levels could promote mammary tissue oncogenic transformation, some molecular markers and morphological characteristics were analyzed in the mammary gland of virgin adult transgenic mice that overexpress GH. For this purpose, mammary gland whole mounts and histological studies were performed. In transgenic mice, whole mounting studies evidenced epithelial ductal elongation and enlarged ducts along with deficient branching and reduced number of lobules compared to control mice. The number of terminal end buds was similar in normal and transgenic breast tissue. Hematoxylin and eosin staining confirmed a reduction in the number of ducts and alveolar structures in transgenic mice, with a significant prevalence of ducts in detriment of lobules. However, in transgenic mice, a thickening in the ductal wall was observed. Immunostaining for ki67 and c-Fos expression were found to be increased in transgenic mice, while c-Jun was decreased and c-Myc showed no significant differences between normal and transgenic tissues. In conclusion, upregulation of GH induces morphological alterations in the mammary gland that affects its normal development. While these effects are non-tumorigenic per se, they might predispose to oncogenic transformation.