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Naoto Yoneda, Minoru Irahara, Seiichiro Saito, Hirokazu Uemura and Toshihiro Aono

Yoneda N, Irahara M, Saito S, Uemura H, Aono T. Usefulness of recombinant human prolactin for treatment of poor puerperal lactation in a rat model. Eur J Endocrinol 1995;133:613–7. ISSN 0804–4643

Recombinant human prolactin (r-hPRL) was produced by a line of murine C127 cells transfected with human PRL gene. To assess the biological efficacy of r-hPRL in vivo, we studied its influence on milk secretion using a rat model in which lactation was reduced by bromocriptine treatment. Puerperal rats were injected daily for 9 days after delivery with bromocriptine or bromocriptine plus r-hPRL, and lactational performance was assessed by weighing the pups. The concentrations of rat and human PRL in rat serum were measured by specific radioimmunoassays and the mammary glands were examined on postpartum day 10. Daily injection of bromocriptine (0.1 mg/rat) significantly reduced the endogenous level of rat PRL and impaired the weight gain of the pups. Administration of r-hPRL increased the serum level of human PRL. Daily injections of r-hPRL (50 μg/rat, twice a day) restored lactational performance and significantly increased the weight of the pups. The detrimental effect of bromocriptine on the mammary glands, assessed by both weight and histological appearance, was reversed by administration of r-hPRL. These results demonstrate that r-hPRL is biologically active in vivo and replacement therapy of r-hPRL is effective in improving the lactational performance in bromocriptine-treated rats, and also that r-hPRL may be useful for the treatment of women with poor lactation.

Naoto Yoneda, Department of Obstetrics and Gynecology, School of Medicine, The University of Tokushima, 3-18-15 Kuramoto, Tokushima 770, Japan

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Toshiyuki Yasui, Ayako Saijo, Hirokazu Uemura, Toshiya Matsuzaki, Naoko Tsuchiya, Mitsutoshi Yuzurihara, Yoshio Kase and Minoru Irahara

Objective

The aim of the present study was to determine the different effects of oral estrogen therapy (ET) and transdermal ET on changes in circulating levels of cytokines and chemokines in relationship to changes in markers of inflammation in postmenopausal women with hysterectomy.

Methods

Fifty-five postmenopausal women with hysterectomy were randomly assigned in open, parallel-group fashion to an oral ET group and a transdermal ET group. Serum levels of cytokines and chemokines were simultaneously measured using a multiplexed human cytokine assay. Serum concentrations of high-sensitive C-reactive protein, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, and E-selectin were measured as vascular inflammation markers.

Results

Both oral ET and transdermal ET significantly decreased serum interleukin (IL)-7 concentrations at 12 months (P=0.020 and P=0.015 respectively). Transdermal ET decreased serum concentrations of IL-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1β (P=0.05, P=0.019, and P=0.029), but oral ET increased IL-8 level (P=0.025). There were significant differences in percentage changes in IL-8 and MIP-1β between the oral and transdermal ET groups. Oral ET significantly decreased E-selectin level after 12 months.

Conclusion

Transdermal ET reduces circulating levels of IL-8, MCP-1, and MIP-1β, while both oral ET and transdermal ET reduce circulating level of IL-7.