Effects of dopamine d2 receptor agonists in a pituitary transplantation-induced hyperprolactinaemia/anovulation model in rats.
1. In the present study, we investigated the effects of hyperprolactinaemia, induced by transplantation of anterior pituitary glands under the kidney capsule in female rats, on the relationship between serum and pituitary concentrations of the gonadotropins and on the oestrous cycle. 2. Rats with pituitary transplants showed increased serum prolactin concentrations and decreased serum concentrations of gonadotropins and increased pituitary concentrations of gonadotropins. Moreover, these rats showed persistent dioestrous and anovulation from 3 to 6 days after transplantation. 3. A single oral administration of cabergoline (at doses between 0.001 and 0.1 mg/kg) dose-dependently inhibited the elevated serum prolactin concentrations in hyperprolactinaemic rats. At 0.1 mg/kg, cabergoline induced a continuous reduction in serum prolactin concentrations for 5 days after administration. Terguride (0.1 mg/kg) and bromocriptine (10 mg/kg) also reduced serum prolactin concentrations at 1 and 3 days after administration. All three dopamine D2 receptor agonists increased serum gonadotropin concentrations and ovarian weight at 3 days after administration. 4. In rats exhibiting anovulation, a single oral administration of any one of the three dopamine D2 receptor agonists dose-dependently restored ovulation and a normal oestrous cycle appeared. Oral administration of cabergoline (0.03 mg/kg) or terguride (0.1 mg/kg) restored ovarian function and abolished the anovulation following a reduction in serum prolactin concentrations. However, bromocriptine (10 mg/kg) did not completely abolish anovulation. Following administration of terguride (0.3 mg/kg) or bromocriptine (30 mg/kg), only one normal oestrous cycle appeared; however, following cabergoline (0.1 mg/kg), two normal oestrous cycles appeared. 5. These results suggest that cabergoline has a potent and long-lasting action as a dopamine D2 receptor agonist and, thus, should be a useful drug for the treatment of galactorrhoea and hyperprolactinaemic amenorrhoea and/or anovulation in humans.
Moro
M
M
Pharmacological Laboratories, Kissei Pharmaceutical Co. Ltd., 4365-1 Kashiwabara, Hotaka-machi, Minamiazumi-gun, Nagano 399-8304, Japan.
Inada
Y
Y
Miyata
H
H
Komatsu
H
H
Kojima
M
M
Tsujii
H
H
D000818:Animals; D000858:Anovulation / Q000097:blood / Q000517:prevention & control*; D001971:Bromocriptine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004971:Estrus / Q000187:drug effects; D005260:Female; D006062:Gonadotropins / Q000097:blood; D006728:Hormones / Q000097:blood; D006966:Hyperprolactinemia / Q000097:blood / Q000517:prevention & control*; D016377:Organ Transplantation / Q000009:adverse effects*; D010902:Pituitary Gland / Q000637:transplantation; D011388:Prolactin / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*
D018491:Dopamine Agonists; D006062:Gonadotropins; D006728:Hormones; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D011388:Prolactin