Hormonal Influences on the Estradiol-Induced and Age-Related Increases of Pituitary Dopamine in C57BL/6J Mice

Abstract

Estradiol (E₂) produces many-fold increases in the dopamine (DA) content of the anterior pituitary and also plays a role in the age-related increase in pituitary DA in female C57BL/6J mice. These studies address the following questions: (1) What are the time and dose characteristics of the E₂-induced increase in pituitary DA and can other gonadal steroids – such as progesterone (P) and 5α-dihydrotestosterone – also influence pituitary DA? (2) Is the age-related increase in pituitary DA due entirely to an increase in the E₂:P ratio seen in aging female mice, or can extra-ovarian factors also play a role? (3) Is the E2-induced (and therefore possibly the age-related) increase in pituitary DA secondary to an E₂-induced increase in serum prolactin? In ovariectomized (OVX) mice, E2 implants increased pituitary DA in a time- and dose-dependent fashion. P implants administered to OVX mice simultaneously with E₂ antagonized the E₂-induced increase in pituitary DA. Daily injections of 5α-dihydrotestosterone given in conjunction with E₂ implants had no effect on basal or E₂-increased pituitary DA in OVX mice. Thus, E₂ is the only gonadal steroid examined which increases anterior pituitary DA. In intact aging mice, P attenuates the age-related increase in pituitary DA, supporting the hypothesis that the increased ratio of E₂:P secreted by the ovaries of aging female mice is responsible for the age-related increase in pituitary DA. However, at advanced ages, intact male mice also showed modest increases in anterior pituitary DA. Therefore, extra-ovarian age changes, perhaps age changes intrinsic to the pituitary, also play a minor role in the age-related increase in pituitary DA. E₂ increases the secretion of prolactin, which can then feed back to increase secretion of DA from the tuberoinfundibular dopaminergic neurons, a source of pituitary DA. To determine if the E₂-induced increase in pituitary DA was secondary to an E₂-induced increase in serum prolactin, OVX mice were given pituitary grafts to increase serum prolactin independently of E₂ treatment. The E₂-induced increase of pituitary DA is not mediated, but can be enhanced by prolactinemia.

Sex and age differences in mice models of effort-based decision-making and anergia in depression: the role of dopamine, and cerebral-dopamine-neurotrophic-factor

“…It seems that, while DA in striatal areas decreases with age (Winner et al 2017 ), DA concentration and DA receptor density increases in the anterior pituitary gland. Old and middle-aged females have higher levels of pituitary DA than younger females and also than young and middle-aged males (Telford et al 1987 ; Kochman et al 1993 ). DA levels in this key area for hormonal regulation could regulate the observed differences between males and females on consumption of sweets.…”

DOPA Accumulates in the Hypothalamic-Hypophysial Portal Vessels and Is Taken into the Anterior Pituitary of NSD-1015-Treated Rodents

“…It is thus likely that the AP, a tissue which lacks TII and which has much lower levels of L-AAAD relative to its DA content [30,31], contains DA that is stored dif ferently than in neural tissues. Nonetheless, as in neural tissues, DA in the AP is depleted rapidly in reserpinetreated rats [32], Several DA pools in the APare indicated by subcellular fractionation [33], kinetics of responses to estradiol [12], and age-related increases in DA [12,13,34], Because PRL secretion can be increased despite con current increases in AP DA [12,13,32,35], the bulk of the DA in the AP may not influence PRL secretion.…”

“…Drinking water was adjusted to pH 2.2 to suppress Pseudomonas infections, as a general precaution [II]. In view of the sensitivity of pituitary' DA to estradiol and progesterone [4,12,13], mice were ovariectomized 3 weeks before experimentation. Mice were anesthetized with 2,2,2-tribromoethanol (Matheson, Coleman, Bell, Norwood, Ohio, USA) and bilaterally ovariectomized.…”

“…Aliquots of the homogenate (5-ul duplicates) were saved for protein assay [15]; the remainder was centrifuged at 1,800 g for 5 min. Supernatants were extracted for catechols by binding to alu mina [12,13,16,17], and analyzed by HPLC using a 5-gm C-18 reversed-phase column and precolumn (Brownlee Labs Inc., Santa Clara, Calif., USA) and an electrochemical detector with a glassy carbon electrode (Bioanalytical Systems, West Lafayette, Ind., USA). The mobile phase and chromatography conditions were as described [12,17] except that the mobile phase was acidified to pH 2.1-2.5 to resolve DOPA.…”