Robert L. Eskay

Innervation of the nucleus of the solitary tract and the dorsal vagal nucleus by thyrotropin-releasing hormone-containing raphe neurons

The nucleus of the solitary tract and the dorsal vagal nucleus are richly innervated by thyrotropin-releasing hormone (TRH)-containing fibers arising from the caudal raphe nuclei. After transection of vertically oriented fibers by a horizontal knife-cut in the medulla oblongata, TRH-staining disappeared from the vagal nuclei while it increased in transected nerve fibers ventral to the knife-cut. TRH-containing cells are mainly located in the nucleus raphe pallidus and raphe obscurus. TRH-containing fibers run dorsally within the raphe and enter the dorsal vagal complex at its rostral tip. Then they turn caudally and send branches laterally. Immediately caudal to the level of the obex, several TRH-containing fibers cross over the central canal. Cells in regions other than the raphe (hypothalamus or other rostral areas, ventrolateral medulla, cranial nerves) must contribute little to the TRH innervation of the nucleus of the solitary tract and dorsal vagal nucleus, since various knife-cuts transecting all above possible connections did not alter the TRH innervation pattern or TRH concentrations of these vagal nuclei.

Distribution of α-melanocyte-stimulating hormone in the rat brain: Evidence that α-MSH-containing cells in the arcuate region send projections to extrahypothalamic areas

Abstract The distribution and concentration of α-MSH in the rodent brain has been determined by radioimmunoassay. The limbic system contained substantial quantities of α-MSH. Forty per cent of the α-MSH present in the brain was localized in the hypothalamus, with the highest concentration of α-MSH in the arcuate nucleus. More than 40% of the extrahypothalamic α-MSH in the brain was found in the following areas: midbrain (16%), preoptic area (13%), septum (7%), and thalamus (7%). To determine the source of the hypothalamic and extrahypothalamic α-MSH, the anterior hypothalamic preoptic area of the brain was surgically separated from more caudal diencephalic structures, and the arcuate region of the hypothalamus was surgically isolated from the remainder of the brain. Following these deafferentations, no significant reduction in hypothalamic α-MSH levels was observed; however, a significant reduction in extrahypothalamic α-MSH levels was demonstrated. This dramatic decrease of α-MSH in extrahypothalamic areas of the rodent brain strongly suggests that the bulk of the extrahypothalamic α-MSH arises from neuronal perikarya in the arcuate region. These findings are consistent with the hypothesis that a population of neuronal cell bodies producing α-MSH originate in the arcuate region of the hypothalamus and that they send axonal projections to many areas of the limbic system and brain stem.

Two chemically and immunologically distinct forms of luteinizing hormone-releasing hormone are differentially expressed in frog neural tissues

Immunoreactive luteinizing hormone-releasing hormone (IR-LRF) has been measured in several neural tissues of the frog Rana catesbeiana and characterized by bioassay, chromatography and immunological analysis. Frog brain contains the mammalian form of LRF (mLRF), whereas, sympathetic ganglia and adrenal glands contain a form of LRF (pLRF) chromatographically and immunologically similar to the IR-LRF found in the central nervous systems of several piscine species. Frog retina contains both mLRF and pLRF, in a ratio of about 1:2. The two forms of LRF are apparently equipotent in their ability to release LH from rat gonadotrophs in vitro. Immunological analysis of the pLRF found in the frog nervous system suggests that it is a decapeptide, like mLRF, with one or more amino acid substitutions in the mLRF molecule.

Thyrotropin releasing hormone in the median eminence is in processes of paraventricular nucleus neurons

Abstract Lesions that destroy the hypothalamic paraventricular nuclei cause TRH levels in the median eminence to fall precipitously. Thus, TRH in the median eminence seems to be provided by neurons in or immediately adjacent to the paraventricular nuclei. This suggestion is consistent with the results of earlier anatomical and physiological studies.

Cytokine-induced activation of the neuroendocrine stress axis persists in endotoxin-tolerant mice

Chronic administration of lipopolysaccharide (LPS) to mice markedly reduced activation of the neuroendocrine stress axis elicited by an acute challenge dose of LPS. LPS-induced elevation in norepinephrine turnover in the hypothalamus showed complete tolerance whereas elevation of plasma corticosterone showed only partial tolerance. Challenge-induced increased turnover of dopamine in hypothalamus persisted in LPS-tolerant animals. Neuroendocrine activation persisted following acute challenge with interleukin-1 and tumor necrosis factor following chronic LPS exposure.

Neurotensin in the rat median eminence: the possible sources of neurotensin-like fibers and varicosities in the external layer

The possible sources of neurotensin-like immunoreactive axons in the median eminence were studied after several experimental surgical approaches including unilateral lateral retrochiasmatic area transection, midsagittal knife cut through the median eminence, complete surgical isolation of the medial basal hypothalamus and bilateral paraventricular nucleus lesions. Both immunohistochemical and radioimmunoassay data demonstrate that neurotensin-containing neuronal somata located in the hypothalamic arcuate nuclei represent the main source of neurotensin occurring in the external zone of the median eminence of the rat: neither the complete isolation of the medial basal hypothalamus nor the transection of the major neuronal input channel to the median eminence in the lateral retrochiasmatic area altered neurotensin-like immunoreactivity in the median eminence; bilateral lesioning of the paraventricular nucleus resulted in insignificant changes of neurotensin level in the median eminence; and two days after lesioning the median eminence an increased amount of retrogradely accumulated neurotensin-like immunoreactivity was found in several perikarya of the arcuate nuclei due to the blockage of axonal transport in the transected fibers. Retrograde accumulation of neurotensin-like material in other cells scattered in the anterior hypothalamus (in the paraventricular, periventricular and anterior hypothalamic nuclei) indicates that in addition to the arcuate neurons these neurons may also participate in the neurotensin innervation of the median eminence.

Adrenergic Regulation of β-Endorphin Secretion from Anterior Pituitary in Conscious Rats: Effects of Thyroid State

In conscious, chronically cannulated, unrestrained rats, systemic administration of catecholamines increases the plasma levels of beta-endorphin-like immunoreactivity (beta Ei). In euthyroid rats, this effect is mediated by both alpha 1 and beta-adrenergic receptors; the rise in plasma beta Ei caused by isoproterenol is blocked by 1 mg/kg propranolol, and the similar effects of norepinephrine and phenylephrine are blocked by 0.1 mg/kg prazosin. Both types of responses are completely suppressed by a 4-h pretreatment of rats with 0.1 mg/kg dexamethasone, indicating the anterior pituitary origin of the beta Ei released. Prior sectioning of the pituitary stalk does not significantly reduce the response to either phenylephrine or isoproterenol, suggesting that both agents act directly on the pituitary. Hypothyroidism induced by surgical thyroidectomy does not influence the beta Ei response to isoproterenol, which remains sensitive to block by propranolol or suppression by dexamethasone. However, neither norepinephrine nor phenylephrine is able to increase plasma beta Ei in the hypothyroid animals. Both isoproterenol and phenylephrine remain fully effective in rats made hyperthyroid by daily injections of 40 micrograms/kg T3 for 4 days. We propose that in unstressed rats catecholamines increase plasma beta Ei by a direct action on the anterior pituitary via either alpha 1- or beta-adrenergic receptors, and that expression of the alpha 1-, but not the beta-adrenergic response is regulated by thyroid hormones.

Release of Hypothalamic Hormones under in Vivo and in Vitro Conditions

The presence in hypothalamic tissue of extractable substances, called releasing factors or hormones, which can either stimulate or repress the release of hormones from the adenohypophysis is well established. Moreover, the activities of these hypothalamic substances have been demonstrated under in vivo as well as in vitro conditions. At least three of these factors, luteinizing hormone releasing hormone (LHRH), thyrotropin releasing hormone (TRH), and somatostatin, have been isolated in pure form and found on analysis to be small peptides (1–4). Their amino acid sequences have been determined, and each has been synthesized. The availability of these synthetic compounds has made it possible to develop sensitive immunoassays for each peptide. As a consequence, it is now feasible to address critically the issue of secretion of these hypothalamic hormones and to test with rigor the question of whether these peptides have significant roles in the physiological regulation of the adenohypophysis.