A Transgenic Mouse Model for Investigating the Response of the Upstream Region of Whey Acidic Protein (WAP) Gene to Various Steroid Hormones

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The limitations of studies of clarification of response elements of whey acidic protein (WAP) gene to hormones using mammary cell lines has been shown. We studied the response of the upstream region (2.6 kb) of WAP to various steroid hormones using gonadectomized mWAP/hGH transgenic mice. Ovariectomy or castration for transgenic mice was performed at 10 days or 30 days post partum. Various steroid hormones were administered daily for 10 days to the gonadectomized transgenic mice after they reached 2 months of age. Prior to the hormonal administration and 24 hr after the final administration, blood was collected and the hGH levels in the plasma was measured by RIA. Daily doses of estradiol-17β were significantly more effective at increasing hGH levels in transgenic females ovariectomized at 10 days post partum than progesterone of an equal dose. A combined dose of progesterone and of estradiol-17β significantly amplified the increase of hGH levels accompanied by the great development of mammary glands, compared to a dose of progesterone alone. Corticosterone induced only a slight increase of hGH, while testosterone had no effect. The doses of gonadal steroid hormones did not induce an increase in hGH levels and development of mammary glands in the castrated transgenic males. The results showed that the response of 5' region of WAP requires at least some extended development of the mammary gland and that the 2.6 kb upstream region of the exogenous WAP gene contained the element responsive to ovarian hormones.