Novel hyperprolactinemia and hyperprolactinemic anovulation model using the cynomolgus monkey (Macaca fascicularis) |
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Authors: | Makoto Moro Ryuzo Torii Hajime Ishii Yoshikuni Tanioka Yoichi Inada Masami Kojima Hirotada Tsujii |
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Institution: | (1) Pharmacology Research R&D, Kissei Pharmaceutical Co. Ltd., Hotaka, Minamiazumi, 399-8304 Nagano, Japan;(2) Institute for Experimental Animals, Shiga University of Medical Science, Seta, Ohtsu, 520-2192 Shiga, Japan;(3) Central Institute for Experimental Animals, Kawasaki, 213-0027 Kanagawa, Japan;(4) Pharmacology Research R&D, Kissei Pharmaceutical Co. Ltd., Hotaka, Minamiazumi, 399-8304 Nagano, Japan;(5) Department of Agricultural Biotechnology, Faculty of Agriculture, Shinshu University, Minamiminowa, Kamiina, 399-4598 Nagono, Japan |
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Abstract: | We investigated the relationship between the menstrual cycle and hormone levels in cynomolgus monkeys, and developed a sulpiride-induced
hyperprolactinemic anovulation model. On this study, we demonstrated the usefulness of the commercial human prolactin immunoradiometric
assay kit for the measurement of cynomolgus monkey serum samples. In the normal menstrual cycle of the cynomolgus monkey,
serum prolactin concentrations were not significantly different between luteal and follicular phases. However, the serum prolactin
concentration tended to elevate at the ovulation stage. And serum progesterone began to increase after an estradiol surge,
and then declined before the ensuing preovulatory rise in estradiol. During the luteal phase, the serum concentration of progesterone
was elevated. Moreover, we aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in the cynomolgus
monkey. The serum prolactin level gradually increased during the twice-daily administration of sulpiride, and the drug produced
as big a response at 5 mg/kg. In this study, the length of the menstrual cycle was approximately 29 days in normal cynomolgus
monkeys. When treatment with sulpiride had been continued for more than one month, serum progesterone and estradiol levels
fell to within the range seen in the follicular phase of the normal cycle, and the absence of ovulation was recognized by
laparoscopy. Moreover, in this period we found that amenorrhea or anovulatory menstruation in the experimental animals. We
could produce an anovulatory model induced by sulpiride repeatedly administered over a long time period. Our findings suggest
that the cynomolgus monkey is useful as a endocrinological model that uses prolactin as a parameter and as an anovulatory
model; thus, it could be a useful model for the hyperprolactinemic amenorrhea and/or anovulation seen in humans. |
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Keywords: | Hyperprolactinemia Anovulation Laparoscopy Cynomolgus monkey |
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