Transplantation of fetal growth hormone-releasing factor-immunoreactive neurons into the ventricular system of adult MSG-treated rats.

Fetal (17-18 days of gestation) mediobasal hypothalamic tissue (MBH) was transplanted into the third ventricle of adult, male rats which had been treated neonatally with monosodium glutamate (MSG). MSG treatment caused a marked reduction of growth hormone-releasing factor-like-immunoreactive (GRF-i) perikarya in the arcuate nucleus and GRF-i fibers in the median eminence (ME), as compared to littermate controls. When normal fetal MBH was transplanted into the third ventricle of MSG recipients, numerous GRF-i perikarya were located within the graft four weeks following surgery. GRF-i fibers in the ME of MSG-treated rats were enhanced when MBH grafts were in close contact with the ME, but not when transplants were located dorsally or rostrally in the third ventricle without making contact with the recipient's ME. Fetal cerebral cortex, which was grafted as a control tissue, did not contain GRF-i neurons. These immunohistochemical results suggest that grafted fetal GRF-i perikarya may contact the recipient's ME to increase the content of GRF previously depleted by exposure to MSG.     

Serum levels of prolactin, LH and LH-RH after ablation of the medial basal hypothalamus.

4 weeks after surgical ablation (MHA) of the medial basal hypothalamus (MBH) in adult male rats, serum levels of prolactin, LH, and LH-RH were determined by radioimmunoassay. Blood samples were obtained by jugular venipuncture under ether anesthesia (designated 'stress' samples) and 30 min after the ether stress by rapid decapitation (designated 'resting samples). 30 min after ether, serum levels of prolactin, LH, and LH-RH in MHA rats were comparable to those of intact and sham-operated controls. Among intact and sham-operated rats, ether elicited an initial increased in prolactin but not in LH or LH-RH. In the MHA group, prolactin levels were also acutely increased, although the increment was not as great as in control groups. The data indicate that considerable basal prolactin and LH secretion persists after MHA, and that this continued secretion may be regulated by neurohoromones such as LH-RH which arise from areas outside the MBH.     

125I-[Tyr0,D-Trp8]somatostatin-14 binding sites in the locus coeruleus of the rat are located on both ascending and descending projecting noradrenergic cells

Radioautographic determinations of 125I-[Tyr0,D-Trp8]somatostatin-14 (125I-SRIF) binding sites were performed on frozen serial sections of the locus coeruleus (LC) of control rats and of rats subjected to either bilateral microinjections of 6 hydroxydopamine (6-OHDA) into the LC or unilateral microinjection into the ascending noradrenergic bundles. These experiments were performed in order to determine whether 125I-SRIF binding was localized to noradrenergic-containing cells and in which regions the cells which contain the binding sites are projecting. The extent of the lesions was assessed by measuring norepinephrine (NE) levels in the hippocampus (88% decrease as compared to sham-operated animals) for bilateral LC lesions and in the frontal cortex (87% reduction vs. contralateral side) for unilateral bundle lesions. In control rats, 125I-SRIF binding sites were restricted to the boundaries of the LC and followed closely the distribution of tyrosine hydroxylase-labeled cells. Three weeks after bilateral injections of 6-OHDA, 125I-SRIF binding decreased by 79% in all regions of the LC. In contrast, unilateral destruction of the ascending noradrenergic bundles resulted in a moderate decrease only in the middle part of the LC with a more important effect in the dorsal (55%) than in the ventral (24%) portion of the nucleus. These data demonstrate that: 1) most SRIF receptors in the LC are located in the vicinity of NE-containing cell bodies and 2) NE-containing cells bearing SRIF receptors project to the forebrain as well as to other terminal areas located more caudally in the brain. These data suggest a general role for SRIF in the control of the multiple functions of the LC.     

Efferent ACTH-IR opiocortin projections from nucleus tractus solitarius: a hypothalamic deafferentation study

The distribution of opiocortin (OR-ir) immunoreactive fibers was examined immunocytochemically throughout the brain in rats following surgical isolation of the arcuate opiocortin-ir neuronal pool in the medial basal hypothalamus (MBH). Fibers which emanate from this pool were completely severed and thus eliminated from the rest of the brain, leaving intact those which can be identified immunocytochemically as opiocortin-ir projections from the medullary pool located in the nucleus tractus solitarius (NTS). These studies reveal a unique organizational pattern of proopiomelanocortin (POMC) peptidergic neuronal systems and demonstrate that several pontine and medullary regions receive projections from both the hypothalamic (arcuate) and medullary (NTS) opiocortin-ir perikarya. Comparative analyses of deafferented and control brains reveal that certain brainstem autonomic centers such as parabrachial (PB), locus coeruleus (LC), nucleus paragiganticellularis (PGi) are recipients of fibers which emanate from both arcuate and NTS opiocortin-ir perikarya. Areas which receive projections from arcuate opiocortin-ir neurons alone include forebrain and hypothalamic nuclei as well as the periaqueductal grey.     

Hypothalamic LHRH and plasma LH levels after electrical stimulation of the deafferented medial basal hypothalamus

The medial basal hypothalamus (MBH) of female rats was surgically isolated on the morning of proestrus and luteinizing hormone (LH) levels in the blood were determined before and after electrochemical stimulation (ECS) of the disconnected arcuate-median eminence (ARC-ME) region either on the same afternoon (Group 1) or on the 5th postoperative day (Group 2). Animals of Groups 3 and 4 were stimulated and sampled for LH on the 5th or 10th postoperative day, respectively, these rats having been primed with 5 micrograms estradiol injected daily throughout the experimental period. ECS resulted in a significant rise of plasma LH level in Group 1 and caused full ovulation as evaluated by the presence of ova found the next morning in the Fallopian tubes. Rats of Groups 2-4 failed to show any changes in plasma LH, and no ovulation was observed following ECS. Immunohistochemical examination of the brains revealed that axons staining for the luteinizing hormone-releasing hormone (LHRH) in the ARC-ME region remained at control levels 3 days after deafferentation (e.g. Group 1), whereas a marked decrease or complete absence of these structures was observed 8 or 13 days following surgical isolation of the MBH (e.g. Groups 2-4). These studies strongly support the view that no LHRH synthesizing perikarya are located within the MBH of the rat.     

Immunohistochemical Distribution and Subcellular Localization of the Somatostatin Receptor Subtype 1 (sst1) in the Rat Hypothalamus

The aim of the present study was to examine the cellular and sub-cellular distribution of the somatostatin (SRIF) receptor subtype sst1 in the rat hypothalamus. Receptors were immunolabeled using an antibody directed against an antigenic sequence in the N-terminus of the receptor. Immunopositive neuronal cell bodies and dendrites were observed throughout the mediobasal hypothalamus, including the medial preoptic area, paraventricular, periventricular, and arcuate nuclei. Immunoreactive axons and axon terminals were also observed in the median eminence, suggesting that sst1 is also located pre-synaptically. Electron microscopic examination of the arcuate nucleus revealed a predominant association of immunoreactive sst1 with perikarya and dendrites. Most immunoreactive receptors were intracellular and localized to tubulovesicular compartments and organelles such as the Golgi apparatus, but 14% were associated with the plasma membrane. Of the latter, 47% were apposed to abbuting afferent axon terminals and 20% localized immediately adjacent to an active synaptic zone. These results demonstrate a widespread distribution of sst1 receptors in rat hypothalamus. They also show that somatodendritic sst1 receptors in the arcuate nucleus are ideally poised to mediate SRIF’s modulation of afferent synaptic inputs, including central SRIF effects on growth hormone-releasing hormone neurons documented in this area.Special Issue Dedicated to Miklós Palkovits.     

Distribution of immunoreactive somatostatin in the primate hypothalamus

Immunocytochemical methods were used to compare the localization of somatostatin (SRIF) in the human and rhesus monkey hypothalamus. The distribution of SRIF-containing cell bodies and fibers is similar in the two species. Perikarya are located predominantly in the periventricular region and to a lesser extent in the ventromedial nucleus. Fibers occur in dense clusters within the periventricular region, ventromedial nucleus, arcuate nucleus, median eminence, and pericommissural area of both species. Analysis of serial sections suggests that fibers originate from cells in the periventricular region, extend ventrally through the ventromedial and arcuate nuclei to terminate around the portal vessels of the infundibular stalk, and thereby participate in the regulation of anterior pituitary function. Somatostatinergic fibers are also found surrounding non-immunoreactive perikarya in the ventromedial nucleus and periventricular region of both primates. This arrangement may support somatostatin's postulated role as a neurotransmitter or neuromodulator. The strong similarity between the localization of hypothalamic SRIF in the human and rhesus monkey supports the use of the rhesus monkey as a model for the study of somatostatin as a neuroendocrine regulatory in the human.     

Early immunohistochemical detection of somatostatin-like and methionine-enkephablin-like neuropeptides in the brain of the migratory locust embryo

The two groups of neurosecretory cells producing neuropeptides related to somatostatin (SRIF) and methionine-enkephalin (met-enkephalin), previously high-lighted in the brain of adult migratory locusts, were detected by immunofluorescent techniques during the embryonic development of these insects. The earliest detection of these neurosecretory products occurred firstly in the terminal arborizations, then in the fibres, and finally in the perikarya. SRIF-like material is present in the corpora cardiaca already four days before hatching, i.e. at two-thirds of embryonic life, whereas immunoreactivity can be detected only after hatching in the perikarya located in the pars intercerebralis. The synthesis of met-enkephalin-like neuropeptide starts in the four cells of this system at least two days before hatching as shown by the immunofluorescence in the terminal arborizations along the tractus I to the corpora cardiaca. SRIF-like and met-enkephalin-like neurosecretory products are synthesized and carried to their release areas whilst the formation of brain structures and of the corpora cardiaca has not yet been completed.     

Adrenalectomy does not affect the nocturnal peak of fos expression within hypothalamic pro-opiomelanocortin neurons

Circulating glucocorticoid (GC) levels are thought to modulate the basal activity of pro-opiomelanocortin (POMC) neurons within the mediobasal hypothalamus (MBH) of the male rat. In a recent study we demonstrated that Fos-immunoreactivity (Fos-IR) was spontaneously induced throughout the dark phase of the light/dark cycle within a large population of these MBH neurons. Here, we have investigated the effect of adrenalectomy on the nocturnal expression of Fos protein within POMC neurons. To this aim, groups of intact (IN), adrenalectomized (ADX) and sham-operated (sham) rats were killed 7 days after surgery (or no surgery) at times when Fos-IR is known to show either nadir (at light offset) or peak (6 h after light offset) values within MBH POMC neurons. Brains were processed for Fos- and/or POMC-immunohistochemistry. The results showed that, at both times studied, 7-day adrenalectomy did not affect the number of POMC/Fos double-stained neurons within the MBH. The rostro-caudal pattern of distribution of such labeled neurons throughout the MBH of ADX rats was also similar to that of IN or sham rats. The present data demonstrate that the nocturnal induction of Fos within MBH POMC neurons is not controlled via the nychtemeral rhythm of secretion of the adrenal gland. Furthermore, this study shows that basal levels of circulating GC do not alter the nocturnal peak of Fos synthesis within POMC neurons.     

Immunocytochemical localization of somatostatin in cell bodies of the rat hypothalamus.

Cell bodies of small to moderate-sized neurons in the female rat hypothalamus were stained specifically for somatostatin (SRIF) by means of the unlabeled antibody-peroxidase-antiperoxidase immunocytochemical method. SRIF-positive perikarya were scattered throughout the periventricular nucleus in a limited region extending from the middle of the optic chiasm to the rostral margin of the median eminence. The same neurons were revealed with either rabbit (R) or guinea pig (GP) anti-SRIF antisera. Positive cell bodies were more readily assessed with GP antibodies because nonspecific background staining was much less with these than with R anti-SRIF. Positive perikarya were not observed in other hypothalamic nuclei and ependymal elements were also immunocytochemically negative.     

Distribution of spinal sensory neurons supplying the adrenal gland in the pig

The present study was aimed at disclosing which spinal ganglia contribute to the innervation of the adrenal gland in the pig with special regard to the morphology and intraganglionic distribution of the primary sensory neurons within these ganglia. To this end, the animals were injected with a retrograde fluorescent neuronal tracer Fast Blue into the left adrenal gland during laparotomy. After a survival period of three weeks, labelled spinal sensory neurons were found in the ipsilateral dorsal root ganglia (approximately 99% of all retrogradely marked neurons). However, single adrenal gland-projecting perikarya were observed also in the contralateral dorsal root ganglia from Th3 to L3. The majority of the retrogradely labelled afferent neurons (above 65% of all Fast Blue-positive (FB+) perikarya) were located in two groups of spinal ganglia (at neuromeres Th6-7 and Th12-14, approximately 18% and 47% of neurons, respectively), forming two distinct multiganglionic centres of origin for this neural pathway. The morphometric evaluation of FB+ neurons revealed that the vast majority of them (approximately 81%) belonged to the class of small-sized perikarya (10-30 microm in diameter), while the medium-sized (diameter 30-80 microm) and large neurons comprised only up to 13% and 6.5% of adrenal gland-projecting neurons, respectively. Furthermore, the analysis of the intraganglionic distribution pattern of the retrogradely labelled cells revealed that the highest number of them was located in the medio-caudal domain of the dorsal root ganglia, irrespective of the neuromere studied. Thus, the present study has revealed sources and morphological characteristic of spinal afferent neurons supplying the porcine adrenal gland, simultaneously pointing out to the characteristic features of their inter- and intraganglionic distribution pattern.     

In-vitro pulsatile luteinizing hormone-releasing hormone output is dependent on hypothalamic region and the stage of the estrous cycle

In the following experiments, the role of the preoptic-suprachiasmatic area (POA-SCN) in the control of luteinizing hormone-releasing (LHRH) release was examined by in vitro superfusion of either mediobasal hypothalamus (MBH) or MBH-POA-SCN fragments obtained from cycling rats killed on various days of the estrous cycle. The lowest level of LHRH output occurred during estrus, highest levels during diestrus, and intermediate levels on proestrus in the MBH-POA-SCN preparation. As expected, significant decreases in LHRH output from the MBH alone occurred during both days of diestrus and on proestrus, as compared to output from the MBH-POA-SCN tissue, since this structure contains most of the LHRH perikarya. However, similar LHRH secretion patterns were detected in estrus from both preparations. The average period of the LHRH pulses for the estrous cycle in the MBH-POA-SCN was 30.9 +/- 1.2 min compared to 97.7 +/- 25.1 min in the MBH, with significant differences occurring on diestrus 2. The increase and extreme variability of the period of LHRH pulses in the MBH region, compared to the MBH-POA-SCN region, suggests that it is the latter region that contains the neural circuits that control the LHRH pulse generator. The LHRH pulse amplitudes from both hypothalamic regions were similar during all phases of the estrous cycle, except diestrus 2, when the LHRH pulse amplitude from the MBH region was significantly lower than the LHRH pulse amplitude from MBH-POA-SCN. The percentage of LHRH released in the MBH did not vary with the estrous cycle, however, in the MBH-POA-SCN significant changes were observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunocytochemical demonstration of growth hormone,prolactin and somatostatin-like immunoreactivities in the brain of larval,young adult and upstream migrant adult sea lamprey,Petromyzon marinus

Summary Growth hormone, prolactin and somatostatinlike immunoreactivities were demonstrated in the brains of larval, young adult (parasitic) and upstream migrant adult sea lampreys, Petromyzon marinus, by means of immunoperoxidase techniques. Growth hormone (GH) and prolactin (PRL) were observed within separate perikarya in the nucleus praeopticus, within fibers in the commissura praeinfundibularis, and in nerve endings within the neurohypophysis of larval and adult-stage lampreys. Cell bodies demonstrating immunoreactive growth hormone were more numerous than those reactive for prolactin. Unlike in the upstream migrant adult lamprey, no GH or PRL was demonstrated in the adenohypophysis of larval or parasitic lamprey.Somatostatin (SRIF)-like immunoreactive neurons were demonstrated in the nucleus commissurae praeinfundibularis, anterior and posterior pars ventralis hypothalami, pars dorsalis thalami, and the tegmentum motorium rhombencephali of larval, parasitic and upstream migrant adult lampreys. Many of the SRIF containing neurons within the hypothalamus were cerebrospinal fluid (CSF)-contacting cells. SRIF fibers were found throughout most of the brain predominating within the nucleus praeopticus, pars ventralis hypothalami, and the nucleus interpeduncularis. No SRIF immunoreactivity was found within the neurophyophysis. The possible functions of these peptides within the brain of the lamprey are discussed.     

Retrovirus-mediated expression of preprosomatostatin in rat pituitary GH3 cells: targeting of somatostatin to the regulated secretory pathway

Somatostatin (SRIF) is a 14-amino acid peptide hormone that is synthesized as part of a larger precursor, prepro-SRIF, consisting of a signal peptide and a proregion of 80-90 amino acids; mature SRIF is located at the carboxyl-terminus of the precursor. We have used a recombinant retroviral expression vector encoding anglerfish prepor-SRIF-I to infect rat pituitary GH3 cells. The aim of these studies was to investigate the intracellular storage and secretion of the total pool of endogenous GH compared to that of SRIF. Several clonal lines of GH3 cells expressing high or low levels of SRIF were treated with TRH, forskolin, or depolarizing concentrations of potassium, and the levels of intracellular and secreted GH or SRIF were determined using highly sensitive RIAs. Approximately 65% of the total GH was secreted basally, whereas less than 20% of the SRIF-immunoreactive material was basally secreted. Forskolin treatment or potassium depolarization stimulated GH release, but only about 50% above basal levels. In contrast, SRIF secretion was stimulated approximately 5-fold in response to these secretagogues. Based on its lower basal rate of secretion compared to GH and its enhanced release in response to a variety of secretagogues, we conclude that the heterologously expressed SRIF is preferentially targeted to the regulated pathway in GH3 cells.     

Axonal tracing of autonomic nerve fibers to the superficial temporal artery in the rat

Summary The origin of nerve fibers to the superficial temporal artery of the rat was studied by retrograde tracing with the fluorescent dye True Blue (TB). Application of TB to the rat superficial temporal artery labeled perikarya in the superior cervical ganglion, the otic ganglion, the sphenopalatine ganglion, the jugular-nodose ganglionic complex, and the trigeminal ganglion. The labeled perikarya were located in ipsilateral ganglia; a few neuronal somata were, in addition, seen in contralateral ganglia. Judging from the number of labeled nerve cell bodies the majority of fibers contributing to the perivascular innervation originate from the superior cervical, sphenopalatine and trigeminal ganglia. A moderate labeling was seen in the otic ganglion, whereas only few perikarya were labeled in the jugular-nodose ganglionic complex. Furthermore, TB-labeled perikarya were examined for the presence of neuropeptides. In the superior cervical ganglion, all TB-labeled nerve cell bodies contained neuropeptide Y. In the sphenopalatine and otic ganglia, the majority of the labeled perikarya were endowed with vasoactive intestinal polypeptide. In the trigeminal ganglion, the majority of the TB-labeled nerve cell bodies displayed calcitonin gene-related peptide, while a small population of the TB-labeled neuronal elements contained, in addition, substance P. In conclusion, these findings indicate that the majority of peptide-containing nerve fibers to the superficial temporal artery originate in ipsilateral cranial ganglia; a few fibers, however, may originate in contralateral ganglia.     

The pancreatic glucagon and C-peptide secretion during hyperinsulinemia in euglycemic glucose clamp with or without somatostatin infusion in normal man

6 normal subjects received two times of 2 hr euglycemic glucose clamp studies (insulin infusion rate 40 mU/M2/min) one with and the other without somatostatin (SRIF) infusion (500 microgram/hr). Serum C-peptide and glucagon levels were measured during clamp to study the sensitivity of pancreatic alpha and beta cells to the suppressive effects of exogenous hyperinsulinemia during normoglycemia in normal subjects and to find whether SRIF had any modulative effects on endocrine pancreas secretion at the status of hyperinsulinemia. The results showed that in normal man the degree of suppression of pancreatic glucagon secretion by hyperinsulinemia (approximately 100 uU/ml) during euglycemic glucose clamp without SRIF infusion was less than that of C-peptide with mean value of 62 +/- 4% of basal glucagon remained at the end of clamp study; while only about 30 +/- 2% of basal C-peptide concentrations remained. But during SRIF infused glucose clamp studies (SRIF was infused from 60 to 120 min), 32 +/- 2% of mean basal C-peptide concentrations and 38 +/- 6% of mean basal glucagon concentrations left at the end of 2 hr clamp studies when serum insulin level was about 100 uU/ml. For the glucose infusion rate (M value), it was significantly greater in our normal subjects in response to insulin + SRIF as compared to insulin alone (12.0 + 0.9 vs 8.8 +/- 1.4; P less than 0.01). We concluded: during hyperinsulinemia (100 uU/ml), the sensitivity of pancreatic alpha cells to insulin seems less than that of beta cells in normal man at normoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiological actions of somatostatin (SRIF) in hippocampus: Anin vitro study

The electrophysiological actions of somatostatin (somatotropin release inhibiting factor; SRIF) were investigated in the in vitro hippocampal slice preparation. Intracellular recordings were obtained from pyramidal neurons in area CA1 in slices of hippocampus from guinea pigs and rabbits. Somatostatin, applied via micropressure ejection to CA1 pyramidal-cell somata, was primarily excitatory. The effects, however, were quite variable, with nearly all cells displaying pronounced tachyphylaxis. A majority of cells was depolarized by SRIF, but hyperpolarizations or biphasic depolarization/hyperpolarization responses were also recorded. Only minimal conductance changes were associated with the SRIF-induced voltage changes. Depletion of SRIF, by injection of the intact animal with cysteamine several hours before preparing slices, resulted in no obvious abnormalities in hippocampal slice electrophysiology. Our results obtained with application of exogenous SRIF are consistent with the concept that SRIF acts as an excitatory neurotransmitter/neuromodulator in hippocampus. However, our attempts to demonstrate endogenous SRIF action have thus far been unsuccessful.     

Ultrastructural parameters of GABA-ergic and non-GABA-ergic synaptic contacts on neurons of the catsubstantia nigra

Nigrothalamic neurons were identified in the reticular part of thesubstantia nigra using labelling by the retrograde axonal transport of horseradish peroxidase. Nine parameters of the synaptic contacts (n=195) were analyzed, including the size and shape of terminals and size and type of synaptic vesicies. Sixty-six percent of axon terminals studied formed symmetric contacts and contained large polymorphic vesicles (group I). Two-thirds of these synapses were located on the distal dendrites, while one-third was distributed on the perikarya and proximal dendrites. Synapses of group II (29% of all synapses analyzed) exhibited asymmetric contacts and contained round agranular vesicles. Among these synapses, 79% were located on the distal dendrites, 19% were located on the proximal dendrites, and only 2% were located on the neuronal perikarya. Axon terminals of group III (5% of total population) exhibited symmetric contact and contained small polymorphic vesicles. High-resolution immunogold EM histochemistry indicated that 63% of the group-I axon terminals were GABA-positive. The majority of synapses on the labelled nigrothalamic neurons (21 contacts of 25) belonged to group I. Among these 21 synapses, 19 were axo-somatic and mostly GABA-positive. Within group II, 30% of synapses showed slightly expressed GABA-positivity.Neirofiziologiya/Neurophysiology, Vol. 27, No. 2, pp. 147–157, March–April, 1995.     

Cytopathological effects of estradiol on the arcuate nucleus of the female rat. A possible mechanism for pituitary tumorigenesis.

Large subcutaneous doses (2 mg/21 days) of estradiol valerate (EV) given over several months will induce a prolactin and growth hormone-secreting pituitary tumor in female rats. The medial basal hypothalami (MBHs) of such EV-treated animals were examined at different time intervals with light and electron microscopes to determine whether EV affects the MBH and to relate any observed effects to the process of tumorigenesis. The MBHs of extensively treated rats exhibited profound glial and neuronal changes. The filament content of astrocytes was greatly increased and large dense pleomorphic inclusions filled both astrocytic perikarya and processes. Degenerating neuronal elements have been observed in the neuropil of extensively treated animals. Dark cells identified as M cells were seen to engage in phagocytosis and were loaded with dense inclusions. Some neurons in MBH contained large quantities of lipofuscin that was different in appearance from that of normal females of the same age. The glial reaction developed gradually. At earlier stages of EV treatment there were fewer reactive glia and these contained fewer inclusions. Myelin figures often occurred in these early inclusions. Reactive glia in EV-treated rats did not appear in the preoptic area, dorsomedial nucleus or lateral hypothalamus but were found in ventromedial nucleus. Retired breeders and starvation-stressed rats resembled normal controls. These pathological changes in MBH may result from a direct effect of EV on the hypothalamus. It is possible that, in addition to its effects on the hypophysis, EV suppresses or injures hypophysiotropic cells in MBH, thus releasing pituitary chromophobes from inhibitory hypothalamic influences. This could result in hypersecretion and neoplasia.     

Measles virus modulates human T-cell somatostatin receptors and their coupling to adenylyl cyclase.

The possible role of immunomodulatory peptide somatostatin (SRIF) in measles virus (MV)-induced immunopathology was addressed by analysis of SRIF receptors and their coupling to adenylyl cyclase in mitogen-stimulated Jurkat T cells and human peripheral blood mononuclear cells (PBMC). SRIF-specific receptors were assayed in semipurified membrane preparations by using SRIF14 containing iodinated tyrosine at the first position in the amino acid chain ([125I]Tyr1) as a radioligand. A determination of receptor number by saturation of radioligand binding at equilibrium showed that in Jurkat cells, MV infection led to a dramatic decrease in the total receptor number. The virus-associated disappearance of one (Ki2 = 12 +/- 4 nM [mean +/- standard error of the mean [SEM]]; n = 4) of two somatostatin binding sites identified in control Jurkat cells (Ki1 = 78 +/- 3 pM and Ki2 = 12 +/- 4 nM [mean +/- SEM]; n = 4) was also observed. Almost identical results were obtained for phytohemagglutinin-activated human PBMC. In the absence of MV infection, two somatostatin binding sites were present (Ki1 = 111 +/- 31 pM and Ki2 = 17 +/- 2 nM [mean +/- SEM]; n = 2), whereas in MV-infected cells, only the high-affinity (Ki1 = 48 +/- 15 pM [mean +/- SEM]; n = 2) binding site remained. In addition, MV infection reinforced the inhibitory effects of SRIF on adenylyl cyclase activity, since maximal inhibition at 1 microM peptide was 11% +/- 4% in control cells versus 25% +/- 3% (P < 0.05) in infected Jurkat cells. Moreover, MV infection severely impaired the capacity of adenylyl cyclase to be activated directly (by forskolin) or indirectly (via Gs protein-coupled vasoactive intestinal peptide receptor). An assessment of [methyl-3H]thymidine incorporation showed that SRIF increased proliferative responses to mitogens only in control cells, not in MV-infected cells. Altogether, our data emphasize that MV-associated alteration of SRIF transduction appears to be related to the loss of SRIF-dependent increase of mitogen-induced proliferation.