Cloning and characterization of the 5′-flanking region of the canine growth hormone gene

• Published in: Molecular and cellular endocrinology Vol. 197; no. 1; pp. 133 - 141
• Main Authors: Lantinga-van Leeuwen, Irma S, Timmermans-Sprang, Elpetra A.P, Mol, Jan A
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 29.11.2002
• Subjects: 5' Flanking Region; Amino Acid Sequence; Animals; Base Sequence; Binding Sites; Cloning, Molecular; Dog; Dogs - genetics; Growth Hormone - chemistry; Growth Hormone - genetics; Growth hormone promoter; Humans; Molecular Sequence Data; Progestins; Promoter Regions, Genetic; Protein Binding; Transcription Factors - metabolism; Dog; Growth hormone promoter; Progestins
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/S0303-7207(02)00257-5

The growth hormone (GH) gene is expressed in a variety of tissues outside the pituitary, including the mammary gland. GH expression in the mammary gland is stimulated by progestins. The local synthesis of mammary GH may provide a highly proliferative environment within the mammary gland that may contribute to the development or progression of mammary tumours. To elucidate the mechanism regulating mammary GH expression, we cloned the 5′-flanking region of the canine GH gene using inverse polymerase chain reaction. Gel-shift experiments showed that several sequences in the 5′-flanking region of the GH gene bind mammary nuclear proteins and may be involved in basal and progesterone-induced mammary GH expression. Sequence analysis and comparison with the GH promoters of human, rat, and mouse genes revealed a number of shared binding sites for transcription factors such as Pit-1, which is involved in pituitary GH expression, and for factors involved in the differentiation of lymphoid cells. Moreover, a putative binding site for the progesterone receptor (PR) was identified in all promoters, indicating that the progestin-induced expression of GH in mammary tissue is most probably a direct effect of activated PRs on the GH gene promoter and that this may occur in various species.