Brain Hormone Research Articles

Hormones and feed intake.

During the several decades that hormones have been considered for roles in the control of feeding, certain ones have gained special attention, although the role assigned to any one hormone has varied from time to time. Three classes of hormones have been considered in this review: gastrointestinal, brain, and pancreatic. Of these classes, two have obtained the most compelling evidence for a physiological role in the control of feeding. CCK, an intestinal and brain hormone, appears to be involved in satiety. Glucagon of pancreatic origin appears also to play an important role in satiety. These hormones, when sequestered by a specific antibody, cause a delay in satiety and thus increase food intake. Insulin, another pancreatic hormone, has been considered for several roles in the control of feeding. Recently, attention has been given to the possibility that insulin of the CSF provides an integrated link between the metabolic state of the adipose tissue and the brain structures concerned with the control of feeding. Thus, insulin may be a primary hormone involved in the maintenance of energy balance or of body-weight. Finally, brain opiate peptides, e.g. dynorphin, are very likely involved in the transmission of information concerned with the interaction of feeding and maintenance of energy balance. Clearly, hormones play primary roles in the control of feeding behaviour and the regulation of energy balance, but much remains to be done to establish their specific actions or components of the associated physiological systems.

Regional localization and subcellular compartmentalization of thyrotropin-releasing hormone in adult human brain.

In the current study, we sought to define the subcellular compartmentalization of thyrotropin-releasing hormone (TRH) in adult human brain tissues. Upon evaluating tissues (3-24 h post mortem) from 62 humans, ranging in age from 5 to 75 years, we found that TRH was widely distributed throughout the brain. The highest TRH concentration (ng/mg protein) was in the stalk-median eminence region of the hypothalamus (19.3 +/- 3.3, mean +/- SE); the TRH concentration in the hypothalamus, exclusive of the stalk-median eminence, was much lower (1.7 +/- 0.2). Substantial quantities of TRH also were detected in the medulla oblongata (0.26 +/- 0.08), mammillary bodies (0.33 +/- 0.25), and optic chiasm (0.14 +/- 0.07). Lower levels of TRH were found in the amygdala (0.060 +/- 0.015) and the corpus striatum (0.033 +/- 0.010). TRH was near or below the limits of detection in tissues of the cerebral and cerebellar cortices, the olfactory bulbs, the pons, and the hippocampus. When homogenates of medial basal hypothalamic tissue (prepared in 0.32 M sucrose-10 microM CaCl2) were fractionated by means of differential centrifugation, most of the TRH was recovered in subcellular particles which were pelleted at 10,000 X g and which contained the highest amounts of occluded LDH activity. When the nuclei-free supernatant fluid (900 X g S) was fractionated on discontinuous sucrose density gradients or continuous sucrose density gradients, most of the TRH was recovered in subcellular fractions containing synaptosomes. The subcellular distribution of TRH appeared to be stable for up to 24 h post mortem in rat and human brain tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrine regulation of spermatogenesis in Nereis diversicolor (annelida polychaeta): experimental study of the control of meiotic differentiation.

In Nereidae, spermatogenesis is regulated by a hormone secreted by the supraesophageal ganglion (brain hormone). The hormonal concentration decreases with worm age. Spermatogonial proliferation in young worms proceeds under a high hormonal level whereas differentiation of spermatozoa in aged worms occurs in the absence of brain hormone. Spermatogonia were removed from the endocrine influence of the brain in vitro by the organ culture method. Isolated parapodia produced spermatozoa after 13 days. Control cultures were obtained by associating a parapodium with the prostomium of a young worm. It seems that the brain hormone inhibits the spermatocyte differentiation since removal of the brain results in increased RNA synthesis, followed by DNA replication, meiosis, and spermiogenesis (Bertout, '83). Modalities of the hormonal control of meiosis, especially at the level of the RNA syntheses related to meiotic differentiation, were investigated. Effects of reintroducing the hormonal influence during meiotic differentiation were studied through parapodium-prostomium associations at various time after the brain inhibition has been lifted. Effects or RNA inhibitors (actinomycin D, alpha-amanitin, cordycepin) were also tested. The results lead us to propose a hypothesis according to which brain hormone would interfere with molecular events related to the transition from the stage of spermatogonial proliferation (mitotic behavior) to the stage of meiotic differentiation (meiotic behavior).

Quantitative Distribution of Neurohypophysial Hormones in Human Brain and Spinal Cord

Publisher Summary The neurohypophysial peptides may have functions within the brain, which are quite distinct from their well-established actions on the kidney and uterus. This chapter presents an overview of the human brain and the spinal cord, using specific radioimmunoassays to determine in a quantitative manner the distribution of both vasopressin and oxytocin. The presence of appreciable quantities of oxytocin, and smaller amounts of vasopressin in the dorsal horn of the cord, in the substantia gelatinosa, the nucleus of the spinal tract of the trigeminal nerve, as well as the solitary tract nucleus, suggests that these neurohypophysial peptides may have a role in modulating sensory afferents to the central nervous system. However, in the human brain the greatest concentration of vasopressin and, to a lesser extent, oxytocin is found in the locus coemleus and periaqueductal grey matter, which, together with their presence in the dorsal nucleus of the vagus and intermediolateral grey column of the cord, suggests that there is a close relationship with the ascending and descending noradrenergic pathways. In the medulla, oxytocin predominates over vasopressin in the dorsal nucleus of the vagus nerve, nucleus solitaries, and nucleus of spinal tract of the trigeminal nerve. While, in the spinal cord, the greatest concentration of the peptides is in the intermediolateral grey column where the amount of oxytocin is four times that of vasopressin.

Ovarian cyclic AMP and response to a brain hormone from the mosquito Aedes aegypti

Cyclic AMP was studied as a potential second messenger in hormone-stimulated ecdysone secretion by isolated mosquito ( Aedes aegypti) ovaries. Saline extracts of whole mosquito heads stimulated increased cyclic AMP content of ovaries and medium only if extracts were heat-treated and/or contained the phosphodiesterase inhibitor methylisobutyl xanthine (MIX). Most of the increase was found in ovaries rather than medium. Saline containing MIX alone stimulated only a slight increase in ecdysone secretion and cyclic AMP content. Cyclic AMP began to accumulate within 30 sec of stimulation by heat-treated head extract containing 0.1 mM MIX, and reached maximum levels within 2 min. Levels declined after 5 min of incubation, but remained high for at least 1 hr. Cyclic AMP increased significantly above background when ovaries were incubated for 2 min with an extract concentration of 0.14 head-eqs/50 μl, but ecdysone secretion increased above background only at or above 0.56 head-eqs/50 μl during 6 hr incubations. An ecdysone-stimulating factor partially purified from extracts by high performance liquid chromatography also stimulated increases in ovarian cyclic AMP. Increasing concentrations of 8-bromo-cyclic AMP stimulated increased ecdysone secretion by isolated ovaries during 18 hr incubations, although the highest concentration stimulated secretion only to about half the maximal level stimulated by head extracts.

Changes in plasma cortisol and progesterone after administration of enkephalins to newborn lambs.

Methionine-enkephalin and leucine-enkephalin were injected into the brachiocephalic artery of lambs at 8-18 days of age. There was a significant increase in the concentration of cortisol in plasma 15-30 min after leucine-enkephalin (10-, 100-, and 500-micrograms bolus). After the 100-micrograms bolus, there was a biphasic response and a second significant rise in cortisol was seen at 90 min. Plasma progesterone was elevated significantly at 15-30 min and at 90 min after the 100- and 500-microgram injections of leucine-enkephalin. Methionine-enkephalin (100 micrograms) produced a transient rise in plasma cortisol at 15-30 min, although the mean concentrations were not statistically different from the control period. We conclude that in newborn lambs, enkephalins may influence adrenal function. It is likely that such an action is secondary to effects on brain or pituitary hormone release.

Growth hormone (GH), thyroid-stimulating hormone (TSH), and luteinizing hormone (LH)-like peptides in the rodent brain: non-parallel ontogenetic development with pituitary counterparts

Brain and anterior pituitary growth hormone (GH), thyroid-stimulating hormone (TSH) and luteinizing hormone (LH) were measured during fetal, neonatal, and pubertal life and into adulthood. Immunoassayable GH and TSH could be found in the fetal whole brain before their detection in the fetal pituitary. Developmental patterns of pituitary and brain hormones differed in that pituitary hormones showed a gradual rise in levels from birth to puberty at approximately 20 days of age. Biochemically similar, brain-based peptides demonstrated a remarkable preparturitional surge in concentrations that was limited to a few days immediately preceding birth. Twenty-four hours after birth, brain GH, TSH, and LH had dropped to levels equal to or less than concentrations in the neonatal pituitary and subsequently rose to adult levels around the time of puberty. In these studies it could be shown that both the placental-fetal barrier and the neonatal blood-brain barrier were intact. These observations indicate the presence of two biochemically and immunologically similar but topographically distinct pools of peptides present in the developing brain and in the anterior pituitary gland.

Variants of alpha-melanocyte stimulating hormone in rat brain and pituitary: Evidence that acetylated α-MSH exists only in the intermediate lobe of pituitary

The alpha-melanocyte stimulating hormone (α-MSH) variants from rat and human pituitary and rat brain have been analyzed in detail by radioimmunoassay (RIA) interfacing with various chromatography systems. No authentic α-MSH was detected in extracts of rat brain regions or human pituitary. In these tissues the only α-MSH variant detected was characterized as des-acetyl α-MSH. Conversely, acetylated α-MSH was found to be the predominant form in rat pituitary. In addition to α-MSH, extracts from both rat and cow pituitary were found to contain an α-MSH variant with the characteristics of an O-N-diacetyl derivative.

Further studies on the identification of neurons containing immunoreactive alpha-melanocyte-stimulating hormone (α-MSH) in the rat brain

In order to identify more accurately the organelles containing immunoreactive α-melanocyte-stimulating hormone (α-MSH) in the rat brain, attempts were made to improve the ultrastructural preservation of the neural tissue used for immunostaining of the peptide. With the post-embedding staining technique, the quality of the preservation was not adequate since only low concentrations (0.2–0.5%) of OsO 4 could be used for postfixation. Higher concentrations of OsO 4 completely destroyed the antigenicity of α-MSH. With the pre-embedding technique in which the immunostaining is performed prior to postfixation with OsO 4, a good preservation could be obtained making possible the identification of organelles and classification of endings containing immunoreactive α-MSH. In the dendrites, the staining was rather diffuse without any clear association with organelles. In the endings, the staining was mostly restricted to dense core vesicles with some degree of diffusion in the cytoplasm. None of the positive endings were seen making synaptic contact. These results support the hypothesis that α-MSH could be released in sites other than the classical synaptic junction and act as a local hormone.

Neuroendocrine control of Na+ balance in the fiddler crab Uca pugilator.

The hemolymph ionic composition and unidirectional Na+ fluxes were analyzed in fiddler crabs (Uca) acclimated to 500 mosmol seawater. Eyestalkless crabs had lower hemolymph osmotic, Na+, and Cl- concentrations. The Na+ efflux was increased from 13.6 +/- 0.6 in control crabs to 19.6 +/- 1.3 mueq.g-1.h-1 in eyestalkless crabs; this increase was shown to be due to a higher Na+ permeability in eyestalkless crabs. Hemolymph Na+ in eyestalkless crabs was increased by an injection of eyestalk extract. The Na+ influx was increased from 11.1 in intact to 15.8 mueq.g-1.h-1 in eyestalkless animals. A kinetic study showed that 1) the influx was higher at all external Na+ concentrations in eyestalkless and intact-Na+-depleted crabs than in intact controls, and 2) the influx mechanism exhibited allosterism. The elevated Na+ influx in eyestalkless crabs was decreased by an injected eyestalk extract. An injected brain extract caused in increase in the Na+ influx in intact animals. It is concluded that the Na+ uptake mechanism is activated by decreasing the hemolymph Na+ concentration and that a brain hormone mediates the effect.

Corrections: Molecular Biology of Brain Hormones

In the Research News article "Molecular biology of brain hormones" (5 Mar., p. 1223) by Gina Kolata, it was stated that the enkephalin precursor codes for ACTH. Rather, ACTH is derived from pro-opiomelanocortin, a different precursor. In addition, Joel Habener's name was misspelled.

Altered imprinting of rat liver monoamine oxidase by o, p'-DDT and methoxychlor

Neonatal administration of o, p'-DDT [1,1,1-trichloro-2-( o-chlorophenyl-2- p-chlorophenyl ethane or methoxychlor resulted in elevated levels of sex-differentiated hepatic monoamine oxidase activities in adult rats, but not in prepubertal animals. Exposure to these hormonally active xenobiotics may have changed the brain hormone environment during the critical period of development, resulting in endocrine alterations that were reflected by latent but permanent increases in hepatic monoamine oxidase activities, i.e. “altered imprinting”. Hepatic glutathione S-transferases and cytochrome P-450 content also underwent sex differentiation, but neonatal treatment with o, p'-DDT or methoxychlor did not alter levels in adult rats. However, glutathione S-transferase activities and cytochrome P-450 content were higher in prepubertal animals treated neonatally with o, p'-DDT. In contrast to monoamine oxidase, effects on glutathione S-transferase activities and cytochrome P-450 content were attributed to induction by these xenobiotics.

Juvenile hormone and the development of ovarian responsiveness to a brain hormone in the mosquito, Aedes aegypti

This study examined the responsiveness of developing ovaries to extracts of heads of the mosquito Aedes aegypti and regulation of that responsiveness by juvenile hormone (JH). Ovaries of 60-hr-old mosquitoes responded to saline extracts of heads in vitro by secreting ecdysone. Ovaries isolated from 12-hr-old females did not respond significantly to extracts, but developed responsiveness in vivo during the previtellogenic phase of growth, 24–60 hr after emergence. Ovaries in abdomens isolated from females (and thus from the source of JH, the corpora allata (CA)) soon after emergence did not grow or become responsive. However, topical application of JH-I or an analog (methoprene) to isolated abdomens induced growth and responsiveness in ovaries, methoprene with greater effect than JH-I. Ovarian growth and responsiveness were functions of the dose of JH-I applied to abdomens. The system predicted results in vivo, as 20-OH-ecdysone content of females CA ablated after emergence increased by only 39 pg-ep when those animals were blood fed, whereas 20-OH-ecdysone in sham-operated or unoperated animals increased 188 pg-eq upon blood feeding.

Distribution of an enzyme which acetylates α-melanocyte stimulating hormone in rat brain and pituitary gland and effects of arcuate nucleus lesions

This study describes the distribution of an α-melanocyte stimulating hormone (α-MSH) acetyltransferase (MAT) in rat brain and pituitary gland. Highest activities of MAT were found in the neurointermediate lobe of the pituitary gland with the anterior lobe containing slightly less. Within the brain, lowest MAT activities were measured in the hypothalamus, the region which contained the highest concentrations of α-MSH. Relatively high enzyme activities of MAT were measured in the hippocampus, cortex and cerebellum—regions with very low α-MSH concentrations. The fact that MAT activity levels did not parallel α-MSH concentrations indicates that MAT was not solely localized to α-MSH synthesizing neurons or endocrine cells. Furthermore, arcuate nucleus lesions which depleted brain α-MSH failed to deplete MAT activity. Although MAT was not solely localized to α-MSH synthesizing cells, it may have functional significance for α-MSH acetylation due to compartmentalization with α-MSH in α-MSH synthesizing endocrine cells and neurons. Alternatively a second regionally specific MAT may exist.

Regional dissociation of histidyl-proline diketopiperazine (cyclo-(His-Pro)) and thyrotropin-releasing hormone (TRH) in the rat brain

The concentrations of cyclo-(His-Pro) and its precursor, thyrotropin-releasing hormone (TRH) were measured in seven different areas of rat brain using specific radioimmunoassays. Although the concentration of both of these peptides was highest in the hypothalamus, their distribution patterns in all other loci of the brain were dissimilar. These results suggest that factors in addition to TRH concentrations are important in determining the unique concentration pattern of cyclo-(His-Pro) in the brain.

The influence of synthetic 6- l-erythrobiopterin on the neurosecretion of the pars intercerebralis of Pieris brassicae

Modifications of the release of neurosecretory products of the pars intercerebralis of larvae of Pieris brassicae are implied by ultrastructural observations after injection of 6- l-erythrobiopterin. A very marked accumulation of granules, especially in the large neurosecretory cells II, is present when animals are kept under short-day conditions which would normally promote release of brain hormone. The possible significance of these observations is discussed.

The distribution and characterisation of thyrotrophin releasing hormone (TRH) in the human brain

Thyrotrophin releasing hormone-like immunoreactivity (TRHLI) extracted from human hypothalamus was found to be homogeneous and identical to authentic TRH in its chromatographic behaviour on reverse-phase high performance liquid chromatography. The majority of extrahypothalamic TRH also behaved as authentic TRH on HPLC. Study of the regional distribution of TRHLI showed a high concentration in the hypothalamus, periaqueductal grey and amygdala, with lower amounts in the basal ganglia and only trace amounts of TRHLI in the cerebral cortex and cerebellum.

Immunohistochemical localization of gonadotropin releasing hormone (GnRH) in the bovine hypothalamus and infundibulum.

Neural structures containing gonadotropin-releasing hormone (GnRH) in the bovine brain and infundibulum were characterized by light microscopic immunohistochemistry. GnRH-positive perikarya were localized singly or in small groups within the infundibular nucleus and were seen grouped in large discrete clusters within the ventromedial nucleus. Positive axons were localized within the brain from the nucleus of the rostral commissure to the medial mammillary nuclei, and in specific areas of the infundibulum and infundibular stalk.

Immunocytochemical localization of luteinizing hormone-releasing hormone (LHRH) in Vibratome-sectioned brain.

Immunocytochemical localization of neuropeptides such as luteinizing hormone-releasing hormone (LHRH) is generally performed on Bouin's fixed tissue sections, following tissue dehydration in alcohols and embedment in paraffin. When the final reaction product accurately reflects content and distribution of the neuropeptide has not been examined carefully. Our data indicate a decrease in radioimmunoassayable LHRH content of brain fixed in Bouin's solution and a further significant reduction following dehydration with alcohol. In order to circumvent this loss of hormone, sections of fixed brain were cut on a Vibratome at 30 micron and collected in phosphate-saline buffer. These Vibratome sections revealed a significantly greater amount of overall immunoreactivity and fiber distribution as compared to paraffin-embedded sectioned tissue. These results suggest that certain neuropeptides, soluble in alcohol, can be extracted during dehydration processes necessary for paraffin embedment.

Action of the brain hormone on the synthesis of “stable” oocyte RNA in Nereidae (annelida polychaeta)

1. 1. In Nereidae , the experimental suppression of the brain hormone activity (brain removal) sets up a diminution of “stable” RNA (18–28 S rRNA, 4–5 S RNA) syntheses, during oogenesis. 2. 2. Quantitative analysis of RNA, carried out on oocytes maintained during 12 days after brain removal, shows a diminution in RNA with regard to the controls. 3. 3. Sedimentation profiles of RNA synthetized after brain removal suggest that an alteration occurs in the processing of 45 S rRNA. 4. 4. The results show that, in Nereidae , the brain hormone controls the storage of “stable” oocyte RNA through an action, not at the transcription level, but on the processing of this RNA.