Rat Anterior Pituitary Dopaminergic Receptors Are Regulated by Estradiol and during Lactation*

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Abstract
We investigated whether dopamine (DA) receptors in rat anterior pituitary change under conditions known to alter PRL secretion. Pituitary donors were males, ovariectomized females, ovariectomized females treated with either 5 μg/kg or 25μg/kg 17β-estradiol benzoate (EB) for 5 days, and lactating rats. Lactating rats either remained with their pups until decapitation or were separated from pups 18 h previously. PRL was analyzed in trunk blood by RIA, and DA receptors were quantitated in partially purified pituitary membranes by equilibrium binding using [3H]spiperone. The number of binding sites (Bmax) and binding affinity (K)d were calculated by Scatchard analyses. Estradiol significantly decreased the Bmax from 359.7 ± 23.0 fmol/mg protein (mean ± SE) in ovariectomized rats to 246.2 ± 19.0 fmol/mg protein with the 5 μg/kg dose and to 179.3 ±10.1 fmol/mg protein with the 25 μg/kg dose. Plasma PRL levels were significantly increased from 16.3 ± 2.0 ng/ml in the ovariectomized rats to 95.8 ± 15.8 ng/ml and 133.4 ± 14.2 ng/ml with the 5 μg/kg and 25 μg/kg doses of EB, respectively. Separation of lactating mothers from pups caused a significant decrease in Bmax (349.5 ± 9.2 fmol/mg protein) as compared with nonseparated mothers (479.9 ± 37.5). Plasma PRL decreased from 531.5 ± 89.5 ng/ml before, to 11.5 ± 2.6 ng/ml after pup separation. Males had low levels of both Bmax (216.1 ± 18.5 fmol/mg protein) and plasma PRL concentration (43.3 ± 7.2 ng/ml). Receptor binding affinity was similar in all groups examined (range, 0.08–0.11 nM). These data indicate that dopaminergic binding sites in the rat anterior pituitary are decreased by estradiol treatment as well as by pup separation from lactating mothers. We postulate that estradiol is responsible for the decrease in dopaminergic receptor density either by acting directly on the pituitary gland or indirectly by increasing DA secretion. However, DA appears to be the major regulating agent of its own receptors after pup separation from lactating mothers. Such changes in the number of dopaminergic binding sites may be an important component in pituitary responsiveness to DA inhibition of PRL secretion during these physiological states.