Comparative Expression Profiling of Lactogenic Hormone Receptor and It’s Signaling Molecules of Bovine Mammary Glands during lactation

Shinichi Yonekura^1,2,3*, Honami Miyazaki², Yukako Tokutake³

¹Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research (ICCER), Shinshu University, Minami-minowa, Nagano, Japan.
²Graduate School of Agriculture, Shinshu University, Minami-minowa, Nagano, Japan.
³Interdisciplinary Graduate School of Science and Technology, Shinshu University, Minami-minowa, Nagano, Japan.

DOI: 10.4236/ojas.2015.52013                

Abstract

Milk synthesis is known to be modulated by peptide hormones such as prolactin (PRL), growth hormone (GH), and insulin-like growth factor I (IGF-I). Previous studies suggested that PRL and IGF-I acted directly on mammary epithelial cells and were involved in lactation. Meanwhile, GH is thought to be indirectly involved in lactation by stimulating the secretion of IGF-I. It is controversial as growth hormone receptors (GHR) is expressed in the mammary epithelial cells. In order to clarify whether GH acted directly on mammary gland tissue, we investigated the prolactin receptors (PRLR), IGF-I receptors (IGF-IR), and GHR as well as the gene expression levels of the downstream signaling molecule for each receptor in the mammary gland tissue of Holstein cows during different stages of lactation. The results revealed that the mRNA expressions of PRLR and IGF-IR were highest during early lactation, and the mRNA expression of the GHR was highest during mid-lactation. We also found that the expression profiling of the signal transducer and activator of transcription 5 (STAT5) genes was similar to that of the GHR gene. On the other hand, the expression profiling of the PRLR gene was similar to that of the SHP2 gene. These results suggest that GH acts on the mammary glands directly, milk synthesis and secretion are chiefly stimulated in mid-lactation, and the timing of the action is different for PRL and IGF-I.

Keywords

Lactation, Growth Hormone, Prolactin, Signal Transduction, Mammary Gland

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Neville, M.C., McFadden, T.B. and Forsyth, I. (2002) Hormonal Regulation of Mammary Differentiation and Milk Secretion. Jounal of Mammary Gland Biology and Neoplasia, 7, 49-66. http://dx.doi.org/10.1023/A:1015770423167
[2]	Bachelot, A. and Binart, N. (2007) Reproductive Role of Prolactin. Reproduction, 133, 361-369. http://dx.doi.org/10.1530/REP-06-0299
[3]	Khandwala, H.M., McCutcheon, I. E., Flyvbjerg, A. and Friend, K.E. (2000) The Effects of Insulin-Like Growth Factors on Tumorigenesis and Neoplastic Growth. Endocrine Reviews, 21, 215-244. http://dx.doi.org/10.1210/edrv.21.3.0399
[4]	Kleinberg, D.L., Ruan, W., Catanese, V., Newman, C. B. and Feldman, M. (1990) Non-Lactogenic Effects of Growth Hormone on Growth and Insulin-Like Growth Factor-I Messenger Ribonucleic Acid of Rat Mammary Gland. Endocrinology, 126, 3274-3276. http://dx.doi.org/10.1210/endo-126-6-3274
[5]	Shushanov, S.S. (2011) Insulin-Like Growth Factors 1 and 2 Regulate Expression of Beta-Casein in Vitro in Mouse Mammary Epithelial Cells. Bulletin of Experimental Biology and Medicine, 152, 202-205. http://dx.doi.org/10.1007/s10517-011-1488-4
[6]	Katoh, K., Komatsu, T., Yonekura, S., Ishiwata, H., Hagino, A. and Obara, Y. (2001) Effects of Adenosine 5’-Triphosphate and Growth Hormone on Cellular H+ Transport and Calcium Ion Concentrations in Cloned Bovine Mammary Epithelial Cells. Journal of Endocrinology, 169, 381-388. http://dx.doi.org/10.1677/joe.0.1690381
[7]	Yonekura, S., Sakamoto, K., Komatsu, T., Hagino, A., Katoh, K. and Obara, Y. (2006) Growth Hormone and Lactogenic Hormones Can Reduce the Leptin mRNA Expression in Bovine Mammary Epithelial Cells. Domestic Animal Endocrinology, 31, 88-96. http://dx.doi.org/10.1016/j.domaniend.2005.09.002
[8]	Bauman, D.E., Eppard, P.J., DeGeeter, M.J. and Lanza, G.M. (1985) Responses of High-Producing Dairy Cows to Long-Term Treatment with Pituitary Somatotropin and Recombinant Somatotropin. Journal of Dairy Science, 68, 1352-1362. http://dx.doi.org/10.3168/jds.S0022-0302(85)80972-3
[9]	Leonard, W.J. and O’Shea, J.J. (1998) Jaks and STATs: Biological Implications. Annual Review of Immunology, 16, 293-322. http://dx.doi.org/10.1146/annurev.immunol.16.1.293
[10]	Schmitt-Ney, M., Doppler, W., Ball, R.K. and Groner, B. (1991) Beta-Casein Gene Promoter Activity Is Regulated by the Hormone-Mediated Relief of Transcriptional Repression and a Mammary-Gland-Specific Nuclear Factor. Molecular and Cellular Biology, 11, 3745-3755.
[11]	Gouilleux, F., Wakao, H., Mundt, M. and Groner, B. (1994) Prolactin Induces Phosphorylation of Tyr694 of Stat5 (MGF), a Prerequisite for DNA Binding and Induction of Transcription. EMBO Jounal, 13, 4361-4369.
[12]	Darvin, P., Joung, Y.H. and Yang, Y.M. (2013) JAK2-STAT5B Pathway and Osteoblast Differentiation. JAKSTAT, 2, e24931. http://dx.doi.org/10.4161/jkst.24931
[13]	Ali, S., Chen, Z., Lebrun, J.J., Vogel, W., Kharitonenkov, A., Kelly, P.A. and Ullrich, A. (1996) PTP1D Is a Positive Regulator of the Prolactin Signal Leading to beta-Casein Promoter Activation. EMBO Journal, 15, 135-142.
[14]	Ram, P.A., Park, S.H., Choi, H.K. and Waxman, D.J. (1996) Growth Hormone Activation of Stat 1, Stat 3, and Stat 5 in Rat Liver. Differential Kinetics of Hormone Desensitization and Growth Hormone Stimulation of Both Tyrosine Phosphorylation and Serine/Threonine Phosphorylation. Journal of Biological Chemistry, 271, 5929-5940. http://dx.doi.org/10.1074/jbc.271.10.5929