Role of hypothalamic inputs in maintaining pituitary-adrenal responsiveness in repeated restraint.

The role of hypothalamic structures in the regulation of chronic stress responses was studied by lesioning the mediobasal hypothalamus or the paraventricular nucleus of hypothalamus (PVH). Rats were acutely (60 min) and/or repeatedly (for 7 days) restrained. In controls, a single restraint elevated the plasma adrenocorticotropin (ACTH), corticosterone, and prolactin levels. Repeated restraint produced all signs of chronic stress, including decreased body and thymus weights, increased adrenal weight, basal corticosterone levels, and proopiomelanocortin (POMC) mRNA expression in the anterior pituitary. Some adaptation to repeated restraint of the ACTH response, but not of other hormonal responses, was seen. Lesioning of the mediobasal hypothalamus abolished the hormonal response and POMC mRNA activation to acute and/or repeated restraint, suggesting that the hypothalamo-pituitary-adrenal axis activation during repeated restraint is centrally driven. PVH lesion inhibited the ACTH and corticosterone rise to the first restraint by approximately 50%. In repeatedly restrained rats with PVH lesion, the ACTH response to the last restraint was reduced almost to basal control levels, and the elevation of POMC mRNA level was prevented. PVH seems to be important for the repeated restraint-induced ACTH and POMC mRNA stimulation, but it appears to partially mediate other restraint-induced hormonal changes.

Anaphylactoid reactions activate hypothalamo-pituitary-adrenocortical axis: comparison with endotoxic reactions.

Infectious and allergic diseases represent distinct aspects of immune response that can be experimentally modeled as endotoxic reactions following bacterial lipopolysaccharide (LPS) administration and anaphylactoid reactions following systemic injection of foreign proteins, respectively. Although it is well established that LPS stimulates the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis, such effects of anaphylactoid reactions are completely unknown. To evaluate the impact of anaphylactoid reactions on HPA regulation, secretion of adrenocorticotropin hormone (ACTH) was followed and the pattern of c-Fos induction in the hypothalamic paraventricular nucleus (PVN) was revealed in rats that were challenged with egg white or compound 48/80. Male rats were intravenously injected with 0.1 ml/100g b.wt. 1:1 diluted egg white or 50 microg/100 g b.wt. compound 48/80, blood samples were taken before and various time intervals between 15-240 min after challenge for plasma ACTH measurement. Anaphylactoid reactions resulted in a rapid, significant activation of ACTH secretion and induced c-Fos immunoreactivity in the corticotropin-releasing hormone (CRH)-secreting subset of the parvocellular neurosecretory neurons. In addition, magnocellular neurosecretory neurons and autonomic-related projection neurons in the PVN became also c-Fos positive upon challenge. Changes in these parameters are compared to those seen in rats challenged with bacterial endotoxin, LPS.

C-kit ligand (Stem Cell Factor) affects neuronal activity, stimulates pituitary-adrenal axis and prolactin secretion in rats.

Stem Cell Factor (SCF) is a potent growth factor affecting proliferation, differentiation and migration as well as secretory functions of various cells of different origin and function. The effect of SCF on neuronal activity and on neuroendocrine regulation has been studied by injecting SCF i.v. into conscious male rats. Administration of SCF elevated adrenocorticotropin (ACTH), corticosterone and prolactin (PRL) plasma levels in a dose-dependent manner. Adrenocorticotropin and corticosterone secretions were maximal after injecting 10 micrograms SCF, while prolactin secretion only reached a maximum at a dose of 20 micrograms. Hormone secretions were maximal at 15 min (ACTH and PRL) or at 30 min (CORT) and declined to the baseline between 90 and 180 min. The functional anatomical approach, using immediate-early gene product c-Fos as a marker of activated neurones, revealed that systemic administration of SCF activated neurosecretory neurones of the hypothalamus in a time-dependent manner. Somatosensory afferent pathways and extrahypothalamic areas--which are involved in the regulation of hypothalamic neurosecretory cells--including various parts of the lamina terminalis, bed nucleus of stria terminalis, central amygdala, locus coeruleus, parabrachial nucleus, nucleus of the solitary tract and ventrolateral medulla also became Fos-positive. As SCF-induced mediators have been suggested to be involved in brain pathophysiology, and as SCF might have been of potential therapeutic use in certain anaemias and leukaemias, the complex interaction between SCF-induced cell-specific actions and its effect on the neuroendocrine system should also be considered.

Effect of pinealectomy and plane of nutrition on wool growth in Merino sheep.

The effects of surgical pinealectomy and plane of nutrition on wool growth and plasma prolactin concentrations in young Merino wethers were investigated. In young pinealectomized wethers maintained at a low live weight under conditions of minimal stress, the decline of conditioned clean wool production on midside patches was slowed when compared to pineal-intact controls. This difference appeared to be due in part to the observed greater secondary wool follicle density in the pinealectomized wethers; mean fiber diameter was affected to a smaller extent, while staple length growth rate was not significantly altered. Circulating prolactin profiles showed a seasonal variation (high in summer, low in winter) in both pinealectomized and control wethers. There was no difference in wool production between pinealectomized and control wethers when the diet of the same wethers was subsequently supplemented with formaldehyde-treated cottonseed meal. While the role of melatonin in the regulation of wool growth remains to be determined, it is suggested that the hormone may have a transient effect on wool production in young wethers under conditions of limited nutrition, but not at higher nutritional levels, and that melatonin may be involved in partitioning of nutrients to the wool follicle.