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.

Influence of antibiotics on IgA and IgG response and persistence of Yersinia enterocolitica in patients with Yersinia-associated spondylarthropathy.

The IgA and IgG antibody response to plasmid-encoded outer membrane proteins was studied in 59 patients with yersinia-associated spondylarthropathy during 15 months of follow-up. Initially, all patients had specific IgA and IgG antibodies to the 36 and 46 kDa and 30% also to the 26 and 58 kDa released proteins, which correlated with the finding of virulent Yersinia bacilli in intestinal biopsies. IgA disappeared in 69% of untreated patients after nine months and persisted in 31% after one year. IgA disappeared within three to six months in 81% of the patients treated with antibiotics for four to six weeks and persisted in 6% after one year (p less than 0.002). IgG antibodies to the 36 and 46 kDa outer membrane proteins persisted in 80% of all patients. Disappearance of IgA was coupled with disappearance of yersinia from intestinal biopsies.

Studies on the mechanism of the selective suppression of plasma levels of follicle-stimulating hormone in the female rat after administration of steroid-free bovine follicular fluid.

Steroid-free bovine follicular fluid (bFF) selectively suppresses the plasma levels of FSH in the female rat, demonstrating that bFF contains inhibin-like material. The present study was concerned with the effects of bFF on the hypothalamic release of LH releasing hormone (LH-RH) into hypophysial stalk blood and on the metabolic clearance rates of gonadotrophins. The metabolic clearance rates of FSH, LH and prolactin were determined after a single injection of and during a constant infusion with adenohypophysial extract. Similar results were obtained with both methods, and treatment with bFF did not alter the metabolic clearance rates of FSH, LH and prolactin. Anaesthesia with urethane, used for surgery involved in the collection of hypophysial stalk blood, did not interfere with the effect of bFF on plasma levels of FSH. The administration of bFF did not change the hypothalamic content of LH-RH, but caused a 30% decrease in the levels of LH-RH in hypophysial stalk plasma. However, a fraction isolated from bFF, which contained 20 times more inhibin-like activity per mg protein than bFF, did not alter the hypothalamic release of LH-RH into the hypophysial portal blood while this fraction was effective in specifically suppressing the plasma levels of FSH. It was concluded that the inhibin-like activity in bFF does not suppress the plasma levels of FSH by affecting its plasma clearance or by influencing the hypothalamic release of LH-RH, but that it has a direct effect on the adenohypophysis in inhibiting the release of FSH. Besides the inhibin-like activity, bFF also contains another factor which can decrease the levels of LH-RH in hypophysial stalk plasma.

Dopaminergic and adrenergic effects on plasma LH levels in rats with hypothalamic islands.

In female rats hypothalamic islands were prepared by making a cut around the mediobasal hypothalamus. Three weeks later the rats were ovariectomized. Two weeks after ovariectomy, part of the animals showed elevated blood LH levels with oscillations, although the mean LH levels were significantly lower than in sham-operated ovariectomized animals. There was a significant correlation between the occurrence of elevated blood LH levels after ovariectomy and the inclusion of at least part of the suprachiasmatic nucleus within the islands. Nor-adrenaline content of the hypothalamus was decreased significantly, but there was no significant change in hypothalamic dopamine content. Injection of doses of apomorphine, ranging form 2.5 microgram/kg to 25 mg/kg sc into island-bearing and sham-operated animals caused a dose-dependent decrease of plasma LH. However, the magnitude of the decrease was smaller in rats with hypothalamic islands than in controls. Even the highest doses of apomorphine did not decrease plasma LH further than to about 100 ng of LH-RP-1/ml. Phenoxybenzamine (10 and 40 mg/kg ip) and phentolamine (20 mg/kg ip) caused a decrease of plasma LH in ovariectomized control rats, but in ovariectomized rats with hypothalamic islands these drugs caused an increase. Clonidine (100 microgram/kg sc followed by 100 microgram/kg ip) had no effect in ovariectomized control rats, but in ovariectomized rats with a hypothalamic island an increase was induced. These results may have been caused by an increased sensitivity of hypothalamic alpha-receptors resulting from severing afferent noradrenergic fibres.