Melatonin-induced downregulation of uterine prolactin receptors in mink (Mustela vison)

A study was conducted to investigate the effects of exogenous melatonin on serum concentrations of estradiol-17β (E₂) and progesterone (P₄) and uterine prolactin (PRL) receptor concentrations in mated mink. In Experiment 1, two groups of adult, standard dark, female mink were mated to fertile males on March 8 or 9. On March 16, mink in group 1 (N = 8) received an empty Silastic implant inserted sc in the interscapular region and served as controls. Mink in group 2 (N = 8) received an implant containing 10 mg crystalline melatonin. On April 2, all animals were lightly anesthetized and blood samples collected via cardiac puncture were analyzed for serum concentrations of E₂ and P₄. Animals were subsequently sacrificed and uterine samples collected for analysis of PRL receptor concentrations. In Experiment 2, adult female mink were assigned randomly to three treatment groups and mated to fertile males between March 6 and 9. On March 16, mink in group 1 (N = 6) received empty Silastic implants and served as controls. Mink in group 2 (N = 6) received a Silastic implant containing 10 mg melatonin. Animals in group 3 (N = 6) received an implant containing 10 mg melatonin and in addition each mink was given daily sc injections of P₄ (1 mg) from March 21 to April 5. At this time the mink were sacrificed, the number of implantation sites recorded, and uteri collected for quantification of PRL receptors. In Experiment 1, exogenous melatonin reduced serum P₄ concentrations to almost nondetectable levels (controls, 8.08 ± 0.73 vs treated, 0.82 ± 0.12 ng/ml; P < 0.001) and resulted in increased concentrations of E₂ (controls, 13.3 ± 1.9 vs treated, 22.0 ± 1.9 pg/ml; P < 0.01). Uterine PRL receptor concentrations decreased (P < 0.05) from 37.74 ± 9.37 fmol/mg protein (controls) to 23.74 ± 9.03 fmol/mg protein in response to melatonin treatment. In those mink treated with melatonin plus P₄ (Experiment 2), uterine PRL receptor concentrations were increased to levels not significantly different than those of controls. None of the mink treated with melatonin alone or in combination with P₄ exhibited implantation. Uteri of mink treated with melatonin or melatonin plus P₄ did not differ in weight but tended to weigh less than uteri of control mink. These data suggest that a high systemic ratio of P₄ to E₂ is essential for production of the uterine PRL receptor in mink and supports the findings of others that implantation in mink cannot be initiated with P₄ alone.