Uteroplacental insufficiency alters the mammary gland response to lactogenic hormones in vitro
Rachael O’Dowd A , Mary E. Wlodek A C and Kevin R. Nicholas BA Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
B Department of Zoology, The University of Melbourne, Victoria 3010, Australia.
C Corresponding author. Email: m.wlodek@unimelb.edu.au
Reproduction, Fertility and Development 20(4) 460-465 https://doi.org/10.1071/RD07228
Submitted: 20 December 2007 Accepted: 18 February 2008 Published: 11 April 2008
Abstract
Adequate mammary development and coordinated actions of lactogenic hormones are essential for the initiation of lactation. Pregnancies compromised by uteroplacental insufficiency impair mammary development and lactation, further slowing postnatal growth. It is not known whether the initiation of lactation or galactopoesis is compromised. Uteroplacental insufficiency induced in rats by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on Day 18 of gestation preceded collection of mammary tissue on Day 20 of pregnancy. Mammary explants were cultured with combinations of insulin, cortisol and prolactin and analysed for α-lactalbumin and β-casein gene expression. Mammary tissue from late pregnant Restricted rats had elevated α-lactalbumin, but not β-casein, mRNA, which is consistent with premature lactogenesis resulting from an early decline in peripheral maternal progesterone. Explants from Restricted rats were more responsive to hormone stimulation after 3 days in culture, indicating that compromised galactopoesis, not lactogenesis, most likely leads to the reduced growth of suckled pups.
Additional keywords: explant, growth restriction, lactation.
Bintarningsih, R. , Lyons, W. M. R. , Johnson, R. E. , and Li, C. H. (1958). Hormonally-induced lactation in hypophysectomized rats. Endocrinology 63, 540–548.
| PubMed |
Kelly, P. A. , Bachelot, A. , Kediza, C. , Hennighausen, L. , Ormandy, C. J. , Kopchick, J. J. , and Binart, N. (2002). The role of prolactin and growth hormone in mammary gland development. Mol. Cell. Endocrinol. 197, 127–131.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Kuhn, N. J. (1969). Progesterone withdrawal as the lactogenic trigger in the rat. J. Endocrinol. 44, 39–54.
| PubMed |
Kulski, J. K. , Nicholas, K. R. , Topper, Y. J. , and Qasba, P. (1983). Essentiality of insulin and prolactin for accumulation of rat casein mRNAs. Biochem. Biophys. Res. Commun. 116, 994–999.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Liu, T. M. Y. , and Davis, J. W. (1967). Induction of lactation by ovariectomy of pregnant rats. Endocrinology 80, 1043–1050.
| PubMed |
Nagaiah, K. , Bolander, F. F. , Nicholas, K. R. , Takemoto, T. , and Topper, Y. J. (1981). Prolactin-induced accumulation of casein mRNA in mouse mammary explants: a selective role of glucocorticoid. Biochem. Biophys. Res. Commun. 98, 380–387.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Nagamatsu, Y. , and Oka, T. (1983). The differential actions of cortisol on the synthesis and turnover of alpha-lactalbumin and casein and on accumulation of their mRNA in mouse mammary gland in organ culture. Biochem. J. 212, 507–515.
| PubMed |
Neville, M. C. , Stahl, L. , Brozo, L. A. , and Lowe-Lieber, J. (1991). Morphogenesis and secretory activity of mouse mammary cultures on EHS. Protoplasma 163, 1–8.
| Crossref | GoogleScholarGoogle Scholar |
Neville, M. C. , McFadden, T. B. , and Forsyth, I. (2002). Hormonal regulation of mammary differentiation and milk secretion. J. Mammary Gland Biol. Neoplasia 7, 49–66.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Nicholas, K. R. , and Hartmann, P. E. (1981). The foetoplacental unit and the initiation of lactation in the rat. Aust. J. Biol. Sci. 34, 455–461.
| PubMed |
Nicholas, K. R. , and Tyndale-Biscoe, C. H. (1985). Prolactin-dependent accumulation of α-lactalbumin in mammary gland explants from the pregnant tammar wallaby (Macropus eugenii). J. Endocrinol. 106, 337–342.
| PubMed |
Nicholas, K. R. , Sankaran, L. , and Topper, Y. J. (1981). The induction of α-lactalbumin in rat mammary explants in the absence of exogenous prolactin: effects of progesterone and estrogen. Endocrinology 109, 978–980.
| PubMed |
Nicholas, K. R. , Sankaran, L. , and Topper, Y. J. (1983). A unique and essential role for insulin in the phenotypic expression of rat mammary epithelial cells unrelated to its function in cell maintenance. Biochim. Biophys. Acta 763, 309–314.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Nicholas, K. R. , Sankaran, L. , Kulski, J. K. , Chomczynski, P. , and Qasba, P. (1988). Comparison of some biological effects of epidermal growth factor and commercial serum albumin on the induction of α-lactalbumin in rat and rabbit mammary explants. J. Endocrinol. 119, 133–139.
| PubMed |
O’Dowd, R. , Kent, J. C. , Moseley, J. M. , and Wlodek, M. E. (2008). Effects of uteroplacental insufficiency and reducing litter size on maternal mammary function and postnatal offspring growth. Am. J. Physiol. Regul. Intergr. Comp. Physiol. 294, R539–R548.
Robinson, G. W. , McKnight, R. A. , Smith, G. H. , and Hennighausen, L. (1995). Mammary epithelial cells undergo secretory differentiation in cycling virgins but require pregnancy for the establishment of terminal differentiation. Development 121, 2079–2090.
| PubMed |
Rothchild, I. , Billiar, R. B. , Kline, I. T. , and Pepe, G. (1973). The persistence of progesterone secretion in pregnant rats after hypophysectomy and hysterectomy: a comparison with pseudopregnant, deciduomata-bearing pseudopregnant, and lactating rats. J. Endocrinol. 57, 63–74.
| PubMed |
Sankaran, L. , and Topper, Y. J. (1988). Progesterone and prolactin are both required for suppression of the induction of rat α-lactalbumin activity. Biochem. Biophys. Res. Commun. 155, 1038–1045.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Shailubhai, K. , Saxena, E. S. , Balapure, A. K. , and Vijay, I. K. (1990). Studies on hormonal modulation of asparagine-linked glycoprotein biosynthesis in explant cultures of rat mammary gland. Indian J. Biochem. Biophys. 27, 425–429.
| PubMed |
Thordarson, G. , Ogren, L. , Day, J. R. , Bowens, K. , Fielder, P. , and Talamantes, F. (1989). Mammary gland development and α-lactalbumin production in hypophysectomized, pregnant mice. Biol. Reprod. 40, 517–524.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Thordarson, G. , Fielder, P. , Lee, C. , Hom, Y. K. , Robleto, D. , Ogren, L. , and Talamantes, F. (1992). Mammary gland differentiation in hypophysectomized, pregnant mice treated with corticosterone and thyroxine. Biol. Reprod. 47, 676–682.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Van Der Schoot, P. , and De Greef, W. J. (1983). Effect of adrenalectomy on the regulation of the secretion of gonadotrophins and prolactin in the lactating rat. J. Endocrinol. 98, 227–232.
| PubMed |
Vermouth, N. T. , and Deis, R. P. (1974). Prolactin release and lactogenesis after ovariectomy in pregnant rats: effect of ovarian hormones. J. Endocrinol. 63, 13–20.
| PubMed |
Warner, B. , Janssens, P. , and Nicholas, K. (1993). Prolactin-independent induction of alpha-lactalbumin gene expression in mammary gland explants from pregnant BALB/c mice. Biochem. Biophys. Res. Commun. 194, 987–991.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wilde, C. J. , Addey, C. V. P. , Bryson, J. M. , Finch, L. M. B. , Knight, C. H. , and Peaker, M. (1998). Autocrine regulation of milk secretion. Biochem. Soc. Symp. 63, 81–90.
| PubMed |
Wlodek, M. E. , Westcott, K. T. , O’Dowd, R. , Serruto, A. , Wassef, L. , Moritz, K. M. , and Moseley, J. M. (2005). Uteroplacental restriction in the rat impairs fetal growth in association with alterations in placental growth factors including PTHrP. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288, R1620–R1627.
| PubMed |
Wlodek, M. E. , Mibus, A. L. , Tan, A. , Siebel, A. L. , Owens, J. A. , and Moritz, K. M. (2007). Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat. J. Am. Soc. Nephrol. 18, 1688–1696.
| Crossref | GoogleScholarGoogle Scholar | PubMed |