Studies were undertaken to characterize the relationship between anterior pituitary dopamine (DA) content and changes in PRL secretion that occur during physiological states in which changes in tuberoinfundibular DA neuronal activity have been previously characterized. The results of these studies are summarized as follows. Serum PRL concentrations and the anterior pituitary DA content were not different between male and diestrous female rats, an unexpected result considering that tuberoinfundibular DA neuronal activity in female rats is 2- to 3-fold greater than that in male rats. The surge of PRL secretion during the afternoon of proestrus was accompanied by a significant decrease in the anterior pituitary content of DA. Increases in PRL secretion that occur early in pregnancy and during suckling were accompanied by a decrease in tuberoinfundibular DA neuronal activity and a decrease in the DA content in the anterior pituitary. Restraint stress increased PRL secretion and reduced the anterior pituitary DA content in both male and female rats, although only female rats respond to immobilization with a decrease in tuberoinfundibular DA neuronal activity. In both male and female aged rats, there were increases in serum PRL concentrations and the anterior pituitary DA content, despite the fact that tuberoinfundibular DA neuronal activity is reduced in the aged rat. Dehydration induced by water deprivation was associated with a small increase in serum PRL concentrations and a large increase in anterior pituitary DA content; similar water deprivation regimens have induced no change in indices of tuberoinfundibular DA neuronal activity. These results demonstrate that there is not a simple relationship among physiologically induced changes in PRL secretion, anterior pituitary DA content, and tuberoinfundibular DA neuronal activity. The results also indicate that the content of DA in the anterior pituitary cannot be used as a reliable index of tuberoinfundibular DA neuronal activity.

cell culture 64 -renin-angiotensin system 340 -stem 457 Bromocriptine

During early pregnancy in the rat, the secretion of prolactin exhibits daily surges which appear to be related temporally to changes in the activity of tuberoinfundibular dopaminergic (TIDA) neurons. The present study was undertaken to determine:(1) the temporal relationships between the cessation of the prolactin surges at midpregnancy and the termination of the semicircadian pattern of TIDA neuronal activity, and (2) if the uterine-placental unit is required for the cessation of these patterns. TIDA neuronal activity was estimated from the rate of dopamine synthesis in the median eminence, which was measured in vivo by determining the rate of DOPA accumulation after the administration of an inhibitor of aromatic L-amino acid decarboxylase. Nocturnal surges of prolactin occurred on days 6–11 of pregnancy but not on days 12 and 13, while diurnal surges occurred on days 6–9. TIDA neurons exhibited a biphasic pattern of activity on days 8–10 of pregnancy with activity being significantly lower at 04.30 h than at 12.00 h. On days 11–13 of pregnancy, this pattern was lost and activity was constantly maintained at the higher values. Nocturnal surges of prolactin that normally cease after day 11 of pregnancy were still observed on days 12 and 13 if the pregnant rats were hysterectomized on day 6. Furthermore, the biphasic pattern of TIDA neuronal activity persisted until day 13 if pregnant rats were hysterectomized on day 6. The administration of bromocriptine, a dopaminergic agonist which in nonpregnant female rats reduces TIDA neuronal activity by virtue of its ability to reduce circulating concentrations of prolactin, reduced TIDA neuronal activity in 6-day pregnant animals, but was ineffective in 13-day pregnant rats. Bromocriptine was, however, able to reduce the activity of TIDA neurons on day 13 if the pregnant rats had been hysterectomized on day 6. These results suggest that at midpregnancy a uterine-placental factor takes over from prolactin in stimulating TIDA neurons; this factor appears to be responsible for terminating the semicircadian pattern of prolactin secretion.

The activities of various dopaminergic neurons in the brain have been estimated biochemically by quantifying the rate of synthesis or turnover of dopamine in brain regions containing the terminals of these neurons. In addition, the activity of tuberoinfundibular dopaminergic neurons have been estimated from the concentration of dopamine in pituitary stalk blood. Manipulations which increase concentrations of prolactin in cerebrospinal fluid or serum (systemic or intracerebroventricular injections of prolactin; injections of dopaminergic antagonists or estrogens; implantation of pituitaries under the renal capsule; prolactin secreting tumors) increase the activity of tuberoinfundibular dopaminergic neurons. The activities of other dopaminergic neuronal systems are not affected by prolactin.

Co-localization of the expression of the dopamine transporter (DAT) with the catecholamine synthesising enzyme tyrosine hydroxylase (TH) has been investigated using transgenic mice expressing Cre recombinase (Cre) dependent green fluorescent protein (GFP) under the control of the DAT promoter (DATIREScre/GFP). Brain sections from adult female mice were stained for Cre-induced GFP and TH using immunohistochemistry, revealing a high degree of co-expression in the midbrain dopaminergic neurons (A8-10) with the exception of the periaqueductal and dorsal raphe nuclei where dual-labelling was notably lower. In contrast, most of the rostral groups of TH-expressing neurons in the forebrain (A11, A13 − A15) showed little or no co-localization with Cre-induced GFP. Interestingly, a subpopulation of about 30% of the TH-immunoreactive neurons in the arcuate nucleus (A12) also express GFP staining. This observation supports the proposal that this hypothalamic cluster of dopaminergic neurons is neurochemically, and thus potentially functionally, heterogeneous. This study extends earlier literature focusing primarily on DAT expression in midbrain structures to demonstrate a heterogeneity of DAT and TH co-localization in forebrain neurons, particularly those in the hypothalamus. It also highlights the importance of carefully selecting and validating transgenic mouse lines when studying dopaminergic neurons.