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C Oliver

Publications and source records attributed to C Oliver.

At least 19 recordsLinked to original sources
PubMed1992

Pre- and post-natal ontogeny of thyrotropin-releasing-hormone in the rat spinal cord: an immunocytochemical study.

This work aimed at providing by means of immunocytochemical techniques a detailed study of the ontogeny of thyrotropin-releasing hormone (TRH) in the spinal cord of the rat. We report the first appearance of TRH-immunoreactive fibers in the ventral funiculus of thoracic and lumbar levels at embryonic day 17. At embryonic day 18, fibers penetrated the ventral gray matter towards the central canal. At embryonic day 19, the first immunoreactive fibers were seen in the intermediolateral cell column at upper thoracic levels. This region was invaded at lower thoracic levels on the day of birth. At this time, TRH-immunoreactive axodendritic synapses were observed in the ventral horn and in the intermediolateral cell column. Immunoreactivity increased in these regions until post-natal day 21 when the adult pattern of TRH immunoreactivity was established in the sympathetic nuclei and in the ventral horn. However, a transient TRH-like immunoreactivity was detected in lamina IIi of the dorsal horn between post-natal days 14 and 30: at ultrastructural level, immunoreactive varicosities were seen to establish axodendritic synapses. In conclusion, TRH is one of the earliest peptidergic systems established in the spinal cord and it presents extensive temporal and topographical similarities with the serotonergic system with which it could be colocalized.

Animals↗
PubMed1992

The rat mast cell antigen AD1 (homologue to human CD63 or melanoma antigen ME491) is expressed in other cells in culture.

Previously we reported that the mAb AD1 recognized a heavily glycosylated 50- to 60-kDa protein (AD1 Ag) sterically close to the high-affinity IgE receptor on rat basophilic leukemia (RBL-2H3) cells. The N-terminal amino acid sequence of the AD1 Ag was nearly identical to that of human CD63 (melanoma-associated Ag ME491). In this study we cloned the cDNA of AD1 Ag from a rat basophilic leukemia 2H3 cDNA library. An open reading frame of 238 amino acids was identified that contained the N-terminal 43 amino acid sequence. No evidence of a signal peptide was found. However, four predominantly hydrophobic stretches of sequence were predicted to form membrane-spanning helices, and three putative N-glycosylation sites were identified. The AD1 Ag and CD63 were highly conserved between rat and human, suggesting that the sequence of this protein is important for its function. By immunostaining various rat tissues, the AD1 Ag was found localized to mast cells. However, it was located to lysosomes, secretory granules and the plasma membrane of RBL-2H3 cells and to lysosomes and plasma membrane of many other cultured cell lines. The AD1 Ag could be induced by placing cells in culture. Fibroblasts and hepatocytes freshly isolated from rat embryos stained very weakly for AD1 Ag; however, after 24 to 48 h in culture they were strongly positive. This increase in the expression of the AD1 Ag was accompanied by an increase in detectable RNA message. Therefore, AD1/ME491/CD63 Ag is a mast cell marker in tissue, but is also associated with other cells in culture.

Amino Acid Sequence↗
PubMed1992

Adherence of rat basophilic leukemia (RBL-2H3) cells to fibronectin-coated surfaces enhances secretion.

Rat basophilic leukemia (RBL-2H3) cells are a useful in vitro model for studies of mast cells and basophils. We examined the adherence of RBL-2H3 cells to different extracellular matrix proteins and the effect of such attachment on secretion. The cells bound to fibronectin-coated surfaces with maximum binding by 1 h at 37 degrees C. There was less attachment to laminin, collagen type I, and collagen type IV. There was no adherence to uncoated surfaces or in the absence of Ca2+. Binding to fibronectin was blocked by a synthetic peptide containing the sequence Arg-Gly-Asp. Therefore, the binding of RBL-2H3 cells to fibronectin may be mediated by surface molecules that belong to the integrin family. Adherence to fibronectin-coated surfaces resulted in cell spreading, a reorganization of the cytoskeletal elements, and a redistribution of the secretory granules. Attachment to fibronectin also dramatically enhanced high affinity IgE receptor-mediated histamine release. This enhancement was maximum by 1 h of adherence and lasted for at least 6 h. There was also enhanced secretion by the Ca2+ ionophore A23187. Thus, adherence to fibronectin can enhance both receptor and non-receptor-mediated release. Addition of soluble fibronectin to RBL-2H3 cells in suspension had no effect on secretion. Therefore, enhanced histamine release required cell attachment to immobilized fibronectin. These results suggest that secretion from mast cells/basophils may be modulated by their interaction with the extracellular matrix.

Animals↗
PubMed1992

Inhibition of IgE binding to RBL-2H3 cells by a monoclonal antibody (BD6) to a surface protein other than the high affinity IgE receptor.

A mAb was isolated (mAb BD6) that recognized a surface glycoprotein on rat basophilic leukemia cells (RBL-2H3). The antibody bound to 2 x 10(6) molecules/cell and specifically blocked IgE binding (50% inhibition with 3.48 +/- 0.51 micrograms/ml; mean +/- SEM), although neither IgE nor anti-high affinity IgE receptor (anti-Fc epsilon RI) mAb blocked mAb BD6 binding to the cells. mAb BD6 did not affect the rate of dissociation of cell-bound IgE, nor did it induce or inhibit the internalization of IgE. mAb BD6 did not release histamine. However, it did cause rapid spreading of the cells. By 1 h the cells had retracted to a spherical shape with their surface covered with membranous spikes, and they could easily be detached from the tissue culture plate. These changes differed from those observed after Fc epsilon RI activation. mAb BD6 immunoprecipitated a complex of two proteins, 38 to 50 kDa and 135 kDa from 125I-surface labeled rat basophilic leukemia cells that are not subunits of Fc epsilon RI. Chemical cross-linking studies showed that these molecules are associated on the cell surface. By immunoblotting, mAb BD6 reacted with a 40-kDa protein. Therefore, mAb BD6 binds to a surface protein that is close to the Fc epsilon RI and sterically inhibits 125I-IgE binding.

Animals↗
PubMed1992

Distribution of thyrotropin-releasing hormone in the rat spinal cord with special reference to sympathetic nuclei: a light- and electron-microscopic immunocytochemical study.

This paper deals with the distribution of thyrotropin-releasing hormone-like immunoreactivity in the spinal cord of the rat, and particularly in the sympathetic nuclei, at light and electron microscopic levels. In the dorsal horn, the inner part of laminae II and III displayed thin thyrotropin-releasing hormone immunoreactive profiles. Electron microscopy revealed small immunoreactive varicosities which made synaptic contact with small dendrites or dendritic spines. Dense thyrotropin-releasing hormone-like immunoreactivity was observed in all sympathetic nuclei (nucleus intermediolateralis pars fascicularis and principalis, nucleus intercalatus and dorsal commissural nucleus) except the nucleus intercalatus pars ependymalis. Electron microscopy showed many immunoreactive varicosities which were often in synaptic contact with dendrites (proximal or distal), rarely with perikarya and never with axons. Sometimes, the same immunoreactive varicosity made axodendritic contacts with two dendrites and, conversely one dendrite was sometimes synaptically contacted by two or more immunoreactive varicosities. The ventral horn displayed a diffuse thyrotropin-releasing hormone-like immunoreactivity except for the cremaster nucleus (at lumbar level) which was densely outlined by immunoreactive profiles. Occasionally a large cell body in lamina IX (a putative motoneuron) was outlined by immunoreactive profiles but ultrastructural studies revealed very few immunoreactive axosomatic synapses, while immunoreactive symmetrical or asymmetrical axodendritic synapses were observed. The present study clearly confirms the existence of thyrotropin-releasing hormone immunoreactive synapses, thus substantiating the physiological role of this hormone in the spinal cord.

Animals↗
PubMed1992

Adrenocorticotropic hormone and beta-endorphin concentrations in the inferior petrosal sinuses in Cushing's disease and other pituitary diseases.

Aim of the present study was the evaluation of ACTH and beta-endorphin-like-immunoreactivity (beta-ELI) in the inferior petrosal sinuses (IPS's) and in the peripheral blood of patients with Cushing's disease (Group 1), with GH- or PRL-secreting adenomas or nontumoral hyperprolactinemia (Group 2). These patients had undergone selective and bilateral simultaneous IPS sampling for diagnostic purposes or for neurosurgical indications. In the patients of Group 1, ACTH and beta-ELI levels were higher in the IPS ipsilateral than in the contralateral to the adenoma and in the periphery (p < 0.001). In the patients of Group 2 ACTH and beta-ELI levels were higher in the IPS's than in the peripheral blood (p < 0.001) and, in the 9 patients with GH- or PRL-secreting adenomas, they were higher in the IPS ipsilateral than in the contralateral to the adenoma and in the periphery (p < 0.05). A significant correlation exists between ACTH and beta-ELI in the periphery (p < 0.01; r = 0.72), in the IPS ipsilateral (p < 0.05; r = 0.54) and contralateral (p < 0.01; r = 0.66) to the adenoma in Group 1, but not in Group 2. In conclusion, higher beta-ELI levels were detected in the IPS's than in the peripheral blood not only in patients with Cushing's disease but also in those with other pituitary diseases not involving ACTH secretion. The absence of correlation between ACTH and beta-ELI in patients not bearing Cushing's disease suggests that in these conditions corticotrophs release ACTH and beta-endorphin in an independent manner.

Adenoma↗
PubMed1992

Acute changes in growth hormone-releasing hormone secretion after injection of BIM 23014, a long acting somatostatin analog, in rams.

BIM 23014 is a somatostatin analog displaying an increased biological half life due to resistance to enzymatic degradation. This peptide inhibits GH release directly at the level of pituitary somatotrophs. In addition, an action of BIM 23014 at the level of the hypothalamus is possible since somatostatinergic fibers and receptors have been identified on GH-RH neurons. To evaluate the effect of BIM 23014 on GH-RH secretion, hypophysial portal blood (HPB) was continuously collected in conscious sheep. Twelve rams (40-45 kg, 9-month-old) with chronically implanted perihypophysial cannulae were i.v. injected with BIM 23014 (1 mg) or saline. HPB and jugular blood were collected for 3-5 hours before and after the injection for the determinations of GH-RH and GH concentrations respectively. The acute injection of BIM 23014 induced a rapid decrease of plasma GH within the first two hours. Simultaneously, GH-RH in HPB decreased significantly. After reaching a nadir, GH concentrations increased to values greater than baseline. A similar rebound in GH-RH levels in HPB was also observed. These data indicate that BIM 23014 acts at the level of GH-RH hypothalamic neurons, in addition to its well-know effect on the pituitary gland.

Animals↗
PubMed1992

Binding of monoclonal antibody AA4 to gangliosides on rat basophilic leukemia cells produces changes similar to those seen with Fc epsilon receptor activation.

The mAb AA4 binds to novel derivatives of the ganglioside Gd1b on rat basophilic leukemia (RBL-2H3) cells. Some of the gangliosides are located close to the high affinity IgE receptor (Fc epsilon RI), and binding of mAb AA4 inhibits Fc epsilon RI-mediated histamine release. In the present study, mAb AA4 was found to bind exclusively to mast cells in all rat tissues examined. In vitro, within 1 min of mAb AA4 binding, the cells underwent striking morphologic changes. They lost their normal spindle shaped appearance, increased their ruffling, and spread over the surface of the culture dish. These changes were accompanied by a redistribution of the cytoskeletal elements, actin, tubulin, and vimentin, but only the actin was associated with the membrane ruffles. Binding of mAb AA4 also induces a rise in intracellular calcium, stimulates phosphatidyl inositol breakdown, and activates PKC. However, the extent of these changes was less than that observed when the cells were stimulated with antigen or antibody directed against the Fc epsilon RI. None of these changes associated with mAb AA4 binding were seen when the cells were exposed to nonspecific IgG, IgE, or four other anti-cell surface antibodies, nor were the changes induced by binding mAb AA4 at 4 degrees C or in the absence of extracellular calcium. Although mAb AA4 does not stimulate histamine release, it enhances the effect of the calcium ionophore A23187 mediated release. The morphological and biochemical effects produced by mAb AA4 are similar to those seen following activation of the cell through the IgE receptor. Therefore, the surface gangliosides which bind mAb AA4 may function in modulating secretory events.

Actins↗
PubMed1992

Ontogeny of prolyl endopeptidase, pyroglutamyl peptidase I, TRH, and its metabolites in rat pancreas.

We demonstrate that two enzymes, soluble unspecific pyroglutamyl peptidase I and prolyl endopeptidase, able to degrade thyrotropin-releasing hormone (TRH) in vitro were present in pancreas at the early stage of rat development. Specific particulate pyroglutamyl peptidase II remained undetectable during ontogenesis. Pyroglutamyl peptidase I specific activity increased until day 3 and decreased after day 5. Furthermore, prolyl endopeptidase specific activity rose slightly to a peak on postnatal day 20. A good correlation between immunoreactive TRH and deaminated TRH (TRH-OH) was found in the 1st wk after birth. However, His-Pro diketopiperazine (DKP) levels were stable and low during development. We show that hot acidic extraction conditions could artefactually generate His-Pro DKP. In vivo, active site-directed inhibitors of pyroglutamyl peptidase I and prolyl endopeptidase enzymes do not show any TRH-deamidating and/or pyroglutamyl peptidase I pathways in neonatal rat pancreas. The data suggest that these two enzymes are not involved in intra- or extracellular control of TRH levels in neonatal rat pancreas and that pancreatic TRH content appears to be principally regulated by biosynthetic steps. Nevertheless, low levels of endogenous His-Pro DKP and TRH-OH identified in neonatal rat pancreas suggest that TRH or TRH-like peptides may be metabolized in this tissue in intact rats, albeit at low rates.

Aging↗
PubMed1992

Effect of diabetes on in vivo and in vitro hypothalamic somatostatin release.

In order to better understand the mechanisms underlying the reduction in growth hormone (GH) secretion in diabetic rats, we studied hypothalamic somatostatin secretion both in vivo (into hypophysial portal blood) and in vitro (from hypothalamic fragments) 5, 9 and 30 days after induction of diabetes. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg. Basal plasma GH was significantly reduced in diabetic rats at all stages. Somatostatin levels in hypophysial portal blood was unaffected in 5-day STZ-diabetic rats and significantly increased 9 days after STZ administration. Chronic insulin replacement therapy in diabetic animals partly normalized somatostatin levels as well as plasma GH and glucose levels. A good correlation was observed between in vivo and in vitro experiments. Indeed, somatostatin release from hypothalamic fragments did not change 5 days after STZ-induced diabetes and significantly increased 9 and 30 days after STZ administration. The in vitro increase in hypothalamic somatostatin secretion was observed in 10 as well as in 33 mM glucose concentration in the incubation medium. In the same experiment, the in vitro hypothalamic corticotropin-releasing factor secretion was lowered 5 and 9 days after diabetes induction. We conclude that hypothalamic somatostatin release increases in diabetic rats. These changes may contribute to the reduction in GH secretion in these animals. However, since these changes occur after the onset of plasma GH decrease, a factor(s) other(s) than somatostatin may play a causal role in the reduction in GH secretion.

Animals↗
PubMed1992

Bilateral and simultaneous inferior petrosal sinus sampling in the early diagnosis of an ACTH-producing pituitary microadenoma and its detection by magnetic resonance one year later.

This study describes a case of pituitary-dependent Cushing's syndrome where standard biochemical and radiological techniques were discordant in localizing the origin of the autonomous adrenocorticotropic hormone (ACTH) hypersecretion in the pituitary. Hormonal evaluation suggested a pituitary genesis for the disease, but both sellar computed tomography and cranial magnetic resonance (MR) were unable to give clear-cut evidence for a pituitary neoplasm. Simultaneous and bilateral inferior petrosal sinus sampling (SBIPS) correctly identified the left side of the pituitary gland as the source of autonomous ACTH production. One year later, the shaded signs of a pituitary lesion in the left side of the gland were seen with MR imaging, and a 0.5-cm in height adenoma was surgically removed. At the 2-year follow-up the patient's symptoms had completely disappeared, and her menses were restored. In this case, SBIPS correctly diagnosed the presence of an ACTH-secreting pituitary microadenoma one year before shaded signs of the pituitary lesion appeared with MR imaging. This is a clear-cut demonstration of the accuracy of the SBIPS technique in localizing small pituitary lesions.

Adenoma↗
PubMed1992

Stimulation of adrenocorticotropin secretion by insulin-induced hypoglycemia in the developing rat involves arginine vasopressin but not corticotropin-releasing factor.

In the neonatal rat, the response of the hypothalamo-pituitary-adrenal axis to stressful stimuli is markedly decreased during the first 2 weeks of life. This peculiar period was named "stress hyporesponsive period." In this report, we studied the effect of insulin-induced hypoglycemia, known as a strong stimulator of the corticotroph function in the adult rat. Rats (8- or 20-day-old) were injected ip with 3 IU/kg synthetic insulin and were killed at various times. In 20-day-old rats, hypoglycemia induced a rapid drop in blood glucose concentrations accompanied by a stimulation of ACTH and corticosterone secretion which reached maximal values within 30 min. On the opposite, in 8-day-old rats, despite a rapid decrease in blood glucose levels, insulin injection induced a gradual rise of plasma ACTH and corticosterone concentrations which peaked at 90 min. This delayed response of the hypothalamo-pituitary-adrenal axis to hypoglycemia in the youngest rats does not seem to be due to a difference of sensitivity to insulin-induced hypoglycemia since injection of increasing doses of insulin (0.3, 0.75, or 3 IU/kg body wt) induced a dose-related decrease of blood glucose concentrations and a rise in plasma ACTH and corticosterone levels, comparable in the two age group studied. Basal or hypoglycemia-stimulated absolute corticosterone values were much lower in 8-day-old rats than in 20-day-old animals, suggesting an immaturity of the adrenal glands in the youngest animals. Daily ACTH injection, starting 3 days before the experiment, had a trophic effect on the adrenal glands leading to a more important increase of corticosterone levels after hypoglycemia in 8-day-old rats. Our results confirm that there is an immaturity of the adrenal glands in young rats, probably due to the low plasma ACTH levels during the neonatal period. To determine the respective role of the two major hypothalamic ACTH secretagogues, we studied the effect of passive immunization against CRF or arginine vasopressin (AVP) on plasma ACTH response after hypoglycemia. Passive immunization against AVP decreased significantly hypoglycemia-stimulated ACTH secretion in both 8- and 20-day-old rats, while no change of plasma ACTH response to insulin injection was observed after passive immunization against CRF. This results suggest that CRF does not seem to be involved in the regulation of ACTH secretion after hypoglycemia in the young rat while AVP seems to be the main hypothalamic stimulatory factor for anterior pituitary corticotrophs response to hypoglycemia during the postnatal period.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Glands↗
PubMed1992

Effect of chronic active immunization with antiarginine vasopressin on pituitary-adrenal function in sheep.

ACTH and cortisol diurnal variations and responses to two types of stress (insulin-induced hypoglycemia and isolation-restraint stress) and to an acute injection of CRF were determined in intact as well as in actively antiarginine vasopressin (AVP)-immunized rams. All immunized sheep developed antibodies to AVP, displayed diabetes insipidus, and looked healthy in spite of their lower gain weight. Basal secretion and diurnal variations of ACTH and cortisol were unaltered in the group of anti-AVP-immunized animals. In contrast, ACTH and cortisol responses to both types of stress and CRF injection were significantly reduced compared to those in controls. These results suggest that endogenous AVP plays a physiological role in the corticotropic response to stress. However, endogenous AVP does not appear to affect basal secretion and diurnal variations of ACTH and cortisol.

Adrenocorticotropic Hormone↗
PubMed1992

Ontogeny of insulin-induced hypoglycemia stimulation of adrenocorticotropin secretion in the rat: role of catecholamines.

We previously reported that insulin-induced hypoglycemia (IIH) induces a large increase in plasma ACTH and corticosterone levels in the developing rat during the stress hyporesponsive period and that this effect is mediated, at least partially, by arginine vasopressin (AVP), but not corticotropin-releasing factor. Nevertheless, ACTH secretion in response to IIH in rats immunoneutralized against AVP was still stimulated, suggesting that other regulatory factors participate in the stimulation of ACTH secretion during IIH. It has been suggested that, in the adult rat, during profound hypoglycemia, epinephrine may act at the pituitary level through beta 2-adrenergic receptors to stimulate ACTH secretion. In this report, we studied the effect of the blockade of beta-adrenergic receptors on the pituitary-adrenal axis response to IIH. Rats (20 or 8 day old) were pretreated with saline or 2.5 mg/kg propranolol (a beta-adrenergic receptors antagonist) and subsequently injected with 3 IU/kg insulin. In 20-day-old rats, insulin injection induced a large increase of plasma ACTH concentrations that were unaffected by propranolol pretreatment. In 8-day-old rats, the IIH-induced increase of plasma ACTH levels was significantly reduced by propranolol pretreatment. Pretreatment of 8-day-old rats with 5 mg/kg CGP 20712A (a selective beta 1-adrenergic receptor antagonist) did not change the plasma ACTH response to insulin injection, while pretreatment with 2.5 mg/kg ICI 118551 (a selective beta 2-adrenergic receptor antagonist) resulted in a significant decrease of the IIH-induced stimulation of ACTH secretion. We next studied the effect of the blockade of circulating AVP and/or beta-adrenergic receptors on the pituitary response to IIH. Pretreatment of 8-day-old rats with antiserum anti-AVP or propranolol was followed by a significant reduction of IIH-induced increase of plasma ACTH concentrations. No additive effect was found after pretreatment with both antiserum anti-AVP and propranolol, suggesting that the stimulatory effect of catecholamines during IIH in 8-day-old rats is mediated through a modulation of hypothalamic AVP secretion.

Adrenergic beta-Antagonists↗
PubMed1992

Effects of metyrapone infusion on corticotropin-releasing factor and arginine vasopressin secretion into the hypophysial portal blood of conscious, unrestrained rams.

The effects of rapid changes of circulating cortisol levels on ACTH secretion and on corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) concentrations into hypophysial portal blood were studied in six adult rams. Pharmacological adrenalectomy was obtained by 3 h metyrapone infusion (100 mg.kg-1.h-1). Blockade of cortisol synthesis induced a tenfold increase of plasma ACTH levels accompanied by a moderate increase of CRF secretion (150% vs preinjection levels) and a large increment of AVP secretion (535% vs preinjection levels). ACTH levels remained high during the 3 h following the end of metyrapone infusion. During the same period, CRF secretion was still elevated (231% vs preinjection levels), while AVP secretion was further stimulated (2,151% vs preinjection levels). Subsequent hydrocortisone infusion (66 micrograms.kg-1.h-1) for 2 h induced a rapid decrease of both ACTH and AVP secretion, while CRF levels in hypophysial portal blood still remained elevated. These data suggest that changes in ACTH secretion induced by acute modifications of the negative glucocorticoid feedback are, in addition to the well documented direct effect of cortisol on the corticotropes, mainly mediated by variations of hypothalamic AVP secretion.

Animals↗
PubMed1992

[Emphysematous cystitis caused by Klebsiella pneumoniae].

Emphysematous cystitis is a very uncommon clinical activity as compared to the high incidence of urinary infections in diabetic patients. The paper explains the pathophysiological mechanisms and updates its clinical and therapeutic diagnostic choices regarding one case of favourable evolution following medical treatment.

Aged↗
PubMed1979

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

The distribution and concentration of alpha-MSH in the rodent brain has been determined by radioimmunoassay. The limbic system contained substantial quantities of alpha-MSH. Forty per cent of the alpha-MSH present in the brain was localized in the hypothalamus, with the highest concentration of alpha-MSH in the arcuate nucleus. More than 40% of the extrahypothalamic alpha-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 alpha-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 alpha-MSH levels was observed; however, a significant reduction in extrahypothalamic alpha-MSH level was demonstrated. This dramatic decrease of alpha-MSH in extrahypothalamic areas of the rodent brain strongly suggests that the bulk of the extrahypothalamic alpha-MSH arises from neuronal perikarya in the arcuate region. These findings are consistent with the hypothesis that a population of neuronal cell bodies producing alpha-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.

Animals↗