Hypothalamic targets for prolactin: assessment of c-Fos induction in tyrosine hydroxylase- and proopiomelanocortin-containing neurones in the rat arcuate nucleus following acute central prolactin administration.

Prolactin (PRL) has been implicated in central actions including those that result in its own regulation and/or the suppression of gonadotropin secretion. It is not clear, however, which neuronal systems may mediate the central effects of PRL. Here, using dual immunohistochemistry for c-Fos and either tyrosine hydroxylase (TH) or proopiomelanocortin (POMC), we have assessed neuronal activation, following centrally administered PRL, within two neuronal networks that have been shown to participate in the inhibitory regulation of reproductive function. Male rats received one intracerebroventricular injection of either PRL (5 microg) or saline (vehicle control) 5 days after cannulae were inserted into the lateral ventricles. Ninety minutes after treatment, animals were perfused with 4% paraformaldehyde, the brains were removed and 30-microm frozen sections were cut throughout the entire hypothalamic region. Parallel sets of sections were processed for both c-Fos immunoreactivity (ir) and either TH-ir or POMC-ir. PRL increased the mean number of c-Fos-ir neurons within the rostral arcuate nucleus (9.3 +/- 2.0 vs. 5.0 +/- 1.2 cells/section, for PRL and control rats, respectively; p < 0.05). Within the TH-ir neurones, PRL induced a significant increase in c-Fos in the dorsomedial portion of the mid-arcuate nucleus (p < 0.05). In contrast, there was no significant increase in the expression of c-Fos within the POMC neurones of the arcuate nucleus. PRL also induced c-Fos expression in the supraoptic nucleus (SON) (11.7 +/- 3.2 vs. 3.0 +/- 1.4 cells/section for PRL and control rats, respectively; p < 0.05), but not in the medial preoptic nucleus, ventromedial nucleus or the dorsomedial nucleus, areas reported to either contain gonadotropin-releasing hormone neurones or express PRL receptors. The results from this study show immediate early gene activation within both the arcuate nucleus and the SON of the hypothalamus following acute PRL administration. While the role of PRL-responsive neurones in the SON remains to be elucidated, these findings support the notion that the central actions of PRL could be mediated via the TH neurones of the dorsomedial arcuate nucleus and/or by a population of neurones in the rostral arcuate nucleus that contain neither TH nor POMC.

The hypothalamus: cross-roads of endocrine and behavioural regulation in grooming and aggression.

Anatomical and functional studies show that the hypothalamus is at the junction of mechanisms involved in the exploratory appraisal phase of behaviour and mechanisms involved in the execution of specific consummatory acts. However, the hypothalamus is also a crucial link in endocrine regulation. In natural settings it has been shown that behavioural challenges produce large and fast increases in circulating hormones such as testosterone, prolactin, corticotropin and corticosterone. The behavioural function and neural mechanisms of such fast neuroendocrine changes are not well understood. We suggest that behaviourally specific hypothalamic mechanisms, at the cross-roads of behavioural and endocrine regulation, play a role in such neuroendocrine changes. Mild stimulation of the hypothalamic aggressive area, produces stress levels of circulating prolactin, corticotropin, and corticosterone. Surprisingly luteinizing hormone does not change. This increase in stress hormones is due to the stimulation itself, and not caused by the stress of fighting. Similar increases in corticosterone are observed during electrical stimulation of the hypothalamic self-grooming area. The corticosterone response during self-grooming-evoking stimulation is negatively correlated with the amount of self-grooming observed, suggesting that circulating corticosterone exerts a negative feedback control on grooming. Earlier literature, and preliminary data form our laboratory, show that circulating corticosterone exerts a fast positive feedback control over brain mechanisms involved in aggressive behaviour. Such findings suggest that the hormonal responses caused by the activity of behaviourally specific areas of the hypothalamus may be part of a regulation mechanism involved in facilitating or inhibiting the very behavioural responses that can be evoked from those areas. We suggest that studying such mechanisms may provide a new approach to behavioural dysfunctions associated with endocrine disorders and stress.