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Horm Metab Res 2005; 37(8): 463-467
DOI: 10.1055/s-2005-870316
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Regulatory Factors on Parathyroid Hormone-related Peptide Production by Primary Culture of Lactating Rat Mammary Gland

H.  Uemura1 , T.  Yasui1 , Y.  Umino1 , M.  Yamada1 , A.  Kuwahara1 , T.  Matsuzaki1 , M.  Maegawa1 , M.  Irahara1
  • 1Department of Obstetrics and Gynecology, University of Tokushima School of Medicine, Tokushima, Japan
Further Information

Publication History

Received 4 October 2004

Accepted after revision 24 March 2005

Publication Date:
01 September 2005 (online)

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Abstract

Parathyroid hormone-related protein (PTHrP) is a major cause of humoral hypercalcemia of malignancy, but has also been widely found in fetal and adult non-neoplastic tissues. Lactating mammary gland has been shown to produce large amounts of PTHrP, and high levels of PTHrP have been measured in milk. We have examined the influences of several substances on the secretion of two different forms of PTHrP by primary cultures of mammary cells isolated from lactating rats to examine the regulatory mechanisms of PTHrP production by mammary cells. Primary cultures of mammary cells seeded at a density of 105 cells per 35 mm culture dish were grown on collagen gels. First, after cells were left 24 hours for attachment and incubated in 2 % FCS containing medium with for 12 hours, PTHrP (1 - 87) secretions were measured in conditioned medium with hormone supplementation for 1, 24 and 48 hours. Progesterone (10 - 7 - 10 - 5 mol/l) significantly suppressed PTHrP (1 - 87) secretion in a dose-dependent manner (p < 0.01), while 17β-estradiol had no influence on PTHrP (1 - 87) secretion. Prolactin, a known stimulator of PTHrP expression in vivo, had no effect in this in vitro model. Second, PTHrP (1 - 34) secretion levels from confluent lactating mammary cells for 24 hours were evaluated. The same results were obtained in the case of PTHrP (1 - 87) secretion from non-confluent cells. Furthermore, dexamethasone (10 - 6 mol/l) significantly suppressed PTHrP (1 - 34) secretion (p < 0.01). These results suggest that PTHrP production from the lactating mammary gland is suppressed by progesterone as well as dexamethasone. Progesterone dramatically falls after delivery, thus possibly accelerating PTHrP production by lactating mammary glands and resulting in considerable amounts of PTHrP secreted into the milk.

Key words

PTHrP - Lactating mammary gland - Progesterone - Dexamethasone

References

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Hirokazu Uemura, M.D., Ph.D.

Department of Obstetrics and Gynecology · University of Tokushima School of Medicine

3-18-15, Kuramoto-cho · Tokushima 770-8503 · Japan

Phone: +81 (88) 633-7177 ·

Fax: +81 (88) 631-2630

Email: uemura@clin.med.tokushima-u.ac.jp