New hyperprolactinemia and anovulation model in common marmoset (Callithrix jacchus) and effect of cabergoline.
We aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in common marmosets. The serum prolactin level gradually increased during the twice-daily administration of sulpiride and reached a plateau after 4 days. Sulpiride produced as big a response at 10 mg kg(-1) as at 50 mg kg(-1). In this study, the length of the ovarian cycle was approximately 30 days in normal common marmosets. Serum progesterone and estradiol levels showed no consistent change during the first 2 months of treatment with sulpiride. When treatment with sulpiride had been continued for more than 2 months, serum progesterone and estradiol levels fell to within the range seen in the follicular phase of the normal cycle and absence of ovulation was recognized by laparoscopy. A single oral administration of cabergoline (at doses between 0.01 and 0.1 mg kg(-1)) dose dependently reduced the elevated serum prolactin level. Bromocriptine (at an oral dose of 10 mg kg(-1)) also reduced the serum prolactin level at 4 and 8 h after its administration. With bromocriptine, the prolactin level had recovered at 24 h, but with cabergoline at doses of 0.05 mg kg(-1) or more, it had still not recovered at 48 h. In anovulatory common marmosets, oral administration of cabergoline at a daily dose of 0.05 mg kg(-1) restored ovarian function and resulted in ovulation in 100% of the group (following a reduction in the serum prolactin level). Bromocriptine at a daily oral dose of 10 mg kg(-1) resulted in ovulation in 67% of the group, but this dose was about 200 times higher than the dose of cabergoline. We could produce an anovulatory model induced by sulpiride repeatedly administered over a long time period. It is suggested that, in this anovulatory model in common marmosets, cabergoline has a potent and long-lasting action as a dopamine D2 receptor agonist, and thus could be a useful drug for the treatment of galactorrhea and hyperprolactinemic amenorrhea and/or anovulation.
Moro
M
M
Pharmacological Laboratories, Kissei Pharmaceutical, Kashiwabara, Nagano, Japan.
Inada
Y
Y
Kojima
M
M
Miyata
H
H
Komatsu
H
H
Torii
R
R
D000818:Animals; D000858:Anovulation / Q000139:chemically induced / Q000188:drug therapy*; D001971:Bromocriptine / Q000494:pharmacology / Q000627:therapeutic use; D000077465:Cabergoline; D002144:Callithrix; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000009:adverse effects; D004873:Ergolines / Q000494:pharmacology* / Q000627:therapeutic use; D004958:Estradiol / Q000097:blood; D005260:Female; D006966:Hyperprolactinemia / Q000139:chemically induced / Q000188:drug therapy*; D008597:Menstrual Cycle / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D011388:Prolactin / Q000097:blood / Q000187:drug effects; D013469:Sulpiride / Q000009:adverse effects; D013997:Time Factors
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004873:Ergolines; D001971:Bromocriptine; D011374:Progesterone; D004958:Estradiol; D013469:Sulpiride; D011388:Prolactin; D000077465:Cabergoline