The complex circumstellar environment of supernova 2023ixf.

The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.

Adrenocorticotropin and beta-lipotropin in the hypothalamus. Localization in the same arcuate neurons by sequential immunocytochemical procedures.

Adrenocorticotropin and beta-lipotropin (beta-LPH) have been localized by immunoperoxidase methods in nerve cells and fibers of the hypothalamus and brain stem of the ewe. 6-mum sections were immunostained first for either ACTH or beta-LPH. The reaction products and the antibody complexes were then eluted completely from the tissue, and the same section was immunostained for the second peptide. Absorption of the primary antisera with a variety of peptide fragments of ACTH and beta-LPH demonstrated, immunocytochemically as well as by radioimmunoassay, that the ACTH and beta-LPH antisera were directed to the COOH- and NH(2)-termini of the peptides, respectively. Neither antiserum recognized any portion of the heterologous peptide. In the sequential staining procedure on the same tissue section, preincubation of the antisera with the homologous peptide abolished the staining, whereas preincubation with the heterologous peptide did not affect it, regardless of the order followed. Every nerve cell in the arcuate nucleus that contained ACTH also contained beta-LPH, but beta-LPH cells appeared, probably falsely, to be twice as numerous as ACTH cells. beta-LPH-positive fibers in and beyond the hypothalamus were also more numerous and stained more intensively than ACTH fibers. The salient exception was fibers in the infundibular zona externa, where the opposite was true. Our observations establish that ACTH and beta-LPH are contained in the same nerve cells They stongly favor biosynthesis in brain, probably from a common precursor molecule, as has been demonstrated in the pituitary gland. The complexity of the cytologic distribution pattern described suggests that the two peptides are not processed in the same manner by the nerve cell.

Renin and angiotensin: the complete system within the neuroblastoma x glioma cell.

Cells of the homogeneous hybrid line neuroblastoma x glioma (NG108-15) have many neuronal properties. Immunocytochemical tests show that they contain both immunoreactive renin and angiotensin; direct radioimmunoassays show that they are positive for renin, angiotensin I, and angiotensin II; enzymatic assays show that they contain angiotensinogen and converting enzyme as well. The renin appears to be present in an enzymatically inactive form that can be activated by trypsin and then blocked by antiserum to purified mouse submaxillary renin. Renin concentration and activity are increased by enhancing cellular differentiation with dibutyryl cyclic adenosine monophosphate or by serum withdrawal. These findings demonstrate a complete renin-angiotensin system within these neuron-like cells, and suggest that activation of intracellular renin could generate angiotensin II.

Mating and pregnancy can occur in genetically hypogonadal mice with preoptic area brain grafts.

Adult female hypogonadal mice, in whom hypogonadism is secondary to a genetic deficiency in hypothalamic gonadotropin-releasing hormone (GnRH), are infertile. Mating, pregnancy, and delivery of healthy litters were achieved after transplantation of normal fetal preoptic area tissue, a major site of GnRH-containing cell bodies, into the third ventricle of adult female hypogonadal mice. Immunocytochemistry revealed GnRH-containing neurons in the grafts and GnRH-containing processes extending to the lateral median eminence of the host brains.

Vasopressin and neurophysin: high concentrations in monkey hypophyseal portal blood.

Vasopressin and its binding protein, neurophysin, were measured by radioimmunoassay in the hypophyseal portal blood of monkeys after cannulation of individual long portal veins. Mean vasopressin concentrations (13,800 picograms per milliliter) in portal blood were more than 300 times as high as those in the systemic circulation (42 picograms per milliliter). Neurophysin concentration was approximately 25 times as high in portal as in systemic blood. By immunoperoxidase techniques, high concentrations of neurophysin were demonstrated around portal capillaries of the median eminence. These studies indicate direct secretion of vasopressin and neurophysin into the portal circulation; the quantities secreted during stress may be sufficient to exert significant effects on secretion of anterior pituitary hormone.

Cerebrospinal fluid and ependymal neurophysin.

Neurophysins are "carrier proteins" associated with vasopressin and oxytocin in the neurohypophyseal system. The release of these hormone associated proteins may serve as an indicator of posterior pituitary function. This report describes the measurement of neurophysin in human and monkey plasma and cerebrospinal fluid (CSF) by radioimmunoassay. Tissue neurophysin is also localized in monkey brain by the immunoperoxidase technique. CSF from 68 patients and five monkeys had easily measurable neurophysin in every sample. The concentration of neurophysin in CSF and in plasma of man is 5.4+/-0.30 ng/ml (mean and SEM) and 0.69+/-0.04, respectively. The two means were significantly different (P < 0.001). In paired plasma and CSF specimens which were obtained simultaneously from each of 13 human and five monkey donors, the concentrations of neurophysin in CSF were greater than those of plasma in every case (paired t test, P < 0.001). Neurophysin administered intravenously to dogs did not enter CSF. Using the immunoperoxidase technique, we found neurophysin not only in the supraoptic and paraventricular nuclei, their tracts, and the posterior pituitary, but also in the specialized ependymal tanycytes of the infundibular recess of the third ventricle and in the external layer of the median eminence where capillaries drain into hypophyseal portal vessels. Neurophysin may pass from CSF to portal vessels via tanycytes in a manner similar to that postulated for releasing factors.

Isolation and characterization of a hormone-producing cell line from human small cell anaplastic carcinoma of the lung.

A continuous cell culture line was established from a bone marrow metastasis of small cell anaplastic carcinoma of the lung. The cultures were characterized by light and electron microscopy, and an unusual concentric arrangement of cells was observed, both in sectioned material from the patient's tumor and from the cell cultures. The cells had two types of specialized cell junctions and contained secretory-like granules of the type described in neuroendocrine cells. Lactic dehydrogenase isozyme patterns were the same as those observed in normal human serum, and the karyotype revealed the presence of several marker chromosomes. Vasopressin was present in the cells and secreted into the culture medium in the absence of neurophysin, as shown by the immunoperoxidase technique and radioimmunoassay. Oxytocin was also absent from cells.

Characterization of complementary deoxyribonucleic acid for precursor of porcine motilin.

Cloned cDNAs encoding the precursor protein for motilin and a novel peptide, motilin-associated peptide, were isolated from a library derived from porcine intestinal mucosa mRNA. Nucleotide sequence analysis predicts a precursor protein of 119 amino acids including a signal peptide in direct linkage with the 22 amino acid sequence for motilin, and a 70 amino acid peptide of unknown function. The putative bioactive moieties are separated by Lys-Lys, dibasic residues that serve as substrates for cleavage by proteolytic maturation enzymes in many polyprotein precursors. While there is an abundant literature detailing a spectrum of tissues and cell types which express motilin like immunoreactivity, analysis of mRNA derived from many of these tissues suggests that the mRNA for the mucosal motilin precursor is only transcribed in this tissue. The nature of the immunoreactive material in the central nervous system and other peripheral tissues remains to be determined.

Chronic syndrome of inappropriate antidiuretic hormone secretion and hypertension in a patient with olfactory neuroblastoma. Evidence of ectopic production of arginine vasopressin by the tumor.

A 28-year-old man with the chronic syndrome of Inappropriate antidiuretic hormone secretion and hypertension was found to have an olfactory neuroblastoma. We demonstrated evidence of elevated circulating arginine vasopressin levels, significantly elevated arginine vasopressin and vasopressin neurophysin levels in the tumor extract, and immunohistochemical staining for arginine vasopressin and vasopressin neurophysin in the tumor cells. The patient's clinical syndrome, including hypertension, resolved following subtotal removal of the tumor and radiation therapy. This study identified olfactory neuroblastoma as a definite cause of ectopic arginine vasopressin secretion causing the syndrome of inappropriate antidiuretic hormone secretion.

Plasma neurophysin levels in monkeys: emphasis on the hypothalamic response to estrogen and ovarian events.

Specific radioimmunoassays for human neurophysins released in response to estrogen (estrogen-stimulated neurophysin, ESN) and nicotine (nicotine-stimulated neurophysin, NSN) have been used to measure two similar neurophysins in rhesus monkey plasma. As in the human, concentrations of rhesus monkey neurophysins in plasma were specifically produced a marked increase of plasma NSN concentrations in the monkey. Estradiol benzoate administered intramuscularly consistently produced an increase in plasma ESN concentrations in normal cycling and castrate monkeys. ESN response to estrogen was exclusively positive and occurred approximately 10 hours after an injection of estradiol benzoate intramuscularly. Plasma samples obtained throughout the mid-cycle were measured and a characteristic rise in estrogen and LH, and a more prolonged rise in ESN were found. Our data indicate that the ESN and LH responses to estrogen stimulation are temporally related events and that the assay of ESN in plasma may be of unique value as it directly reflects the hypothalamic response to changes in estrogen secretion.

Neurosecretory pathways in the mallard duck (Anas platyrhynchos) brain: localization by aldehyde fuchsin and immunoperoxidase techniques for neurophysin (NP) and gonadotrophin releasing hormone (Gn-RH).

Localization studies of the hypothalamohypophysial and tuberoinfundibular neurosecretory systems were performed in the adult male mallard duck with an immunoperoxidase techinque for the demonstration of neurophysin (NP) and gonado-tropin-releasing hormone (Gn-RH) and with aldehyde fuchsin for the staining of neuosecretory material (NSM). A comparison was made between the distribution of NSM stained with aldehyde fuchsin and NP seen by immunocytochemistry. The magnocellular perikarya of the supraoptic (SON) and paraventricular (PVN) nuclei, the zona externa of the anterior median eminence (ME), the fiber layer of both the anterior and posterior ME, and small neurons in the tractus quintofrontalis were stained by both the immunoperoxidase method for NP and by the aldehyde fuchsin stain. In contrast, the parvocellular neurons of the PVN, extra-hypothalamic neurosecretory fibers dorsal to the anterior commissure in the septal region and tanycytes lining the ventral 1/3 of the third ventricle at the level of the anterior ME, were stained only by the immunocytochemical procedure for NP. These observations indicate that immunocytochemistry is more sensitive than aldehyde fuchsin staining for detecting low concentrations of NP in cells and tissues, but the two techniques produce comparable results where the concentration of the NP is relatively high. Two populations of beaded axons containing Gn-RH were distributed throughout the zone externa of both the anterior and posterior ME. One group of fibers paralleled the hypothalamo-hypophysial neurosecretory tract whereas the other was distributed in the contact zone of the ME. Immunoreactive Gn-RH was found in the cytoplasm of a sparse population of cell bodies in the dorsolateral portion of the arcuate nucleus as well as in the axons that project from this nucleus ventrally towards the ME.

Ovarian modulation of immunoreactive gonadotropins-releasing hormone (Gn-RH) in the rat brain: evidence for a differential effect on the anterior and mid-hypothalamus.

Gonadotropins-releasing hormone (Gn-RH) in selected regions of the female rat brain was measured by radioimmunoassay. Detectable immunoreactive Gn-RH was found in the anterior hypothalamic-septal region and in the mid-hypothalamic (arcuate-median eminence) region. Gn-RH was several times higher in the middle region than in the anterior region. Gn-RH was undetectable in the posterior hypothalamic region, frontal cerebral cortex and pineal glands, as well as in random blood samples, and low to undetectable in anterior pituitary glands. Gn-RH activity varied during the estrous cycle and after castration. In the mid-hypothalamic region, Gn-RH content was lowest throughout diestrus and in late morning and early afternoon of proestrus, and highest early in the morning of proestrus and during estrus. A significant decrease at mid-day was only found on the day of proestrus, a few hours prior to the critical period for LH release. In the anterior hypothalamic region, low Gn-RH activity was found from 1200 h of estrus to 1200 h of diestrus-2. A comparatively higher activity was seen at 1700 h of diestrus-2 and also from 1400 h of proestrus to 0800 h of estrus. Twenty-one days after ovariectomy, Gn-RH in the mid-hypothalamic region was significantly lower than the lowest values seen during the estrous cycle, while Gn-RH in the anterior hypothalamic region remained between low and high values seen during the cycle, being significantly higher than the low values. The changes observed during the estrous cycle and after castration suggest that gonadal steroids play a direct role in the control of hypothalamic Gn-RH. These data also demonstrate that Gn-RH varies in a different way in the anterior and mid-hypothalamic regions.

Plasma neurophysin and vasopressin in the rat: response to adrenalectomy and steroid replacement.

Impaired excretion of a water load is known to occur in adrenal insufficiency and to be corrected by administration of glucocorticoid. Such impairment has been related to either a loss of a permissive effect of glucocorticoids on the diluting segments of the nephron or to an alteration of release, turnover, or action of antidiuretic hormone. Specific and sensitive RIAs for arginine vasopressin and neurophysin were utilized to measure plasma and pituitary levels of neurohypophyseal peptides at baseline and after an intragastrically administered water load. Conscious, unanesthetized, and nonstressed sham-operated, adrenalectomized, and adrenalectomized prednisone-treated rats were studied. The results demonstrate a significant elevation in vasopressin and neurophysin in plasma in adrenalectomized rats maintained in a normal state of hydration. After water loading, the adrenalectomized rats diluted their plasma osmolality but had a decreased urinary volume, increased urinary osmolality, and elevated vasopressin and neurophysin in their plasma. In the pituitary, vasopressin and neurophysin were depleted in adrenalectomized rats, indicating increased secretion of these peptides. It is concluded that elevated vasopressin in plasma may be an important factor in the incomplete water diuresis in adrenal insufficiency.

The distribution of luteinizing hormone-releasing hormone (LHRH) in the hypothalamus of the rhesus monkey. Light microscopic studies using immunoperoxidase technique.

Neural structures containing LHRH were characterized in the hypothalamus of the rhesus monkey by four different antisera to the hormone and an immunoperoxidase technique. Immunoreactive perikarya were present in a continuum from the septal-preoptic region anteriorly to the premammillary nucleus posteriorly. These cells were more concentrated in the pericommissural and tubero-infundibular regions. Reactive axons in the median eminence appeared to originate from the positive perikarya in the medial basal hypothalamus; this projection forms a tubero-infundibular tract containing LHRH. In addition, substantial numbers of fibers which entered the median eminence continued down the infundibular stalk and into the posterior pituitary. Other axons appeared to originate in the pericommisural region and projected to the organum vasculosum of the lamina terminalis. Scattered positive fibers were also present in other hypothalamic areas, especially in the periventricular zone and medical mammillary nucleus.

The hypothalamic-neurohypophysial system of the rat: localization and quantitation of neurophysin by light microscopic immunocytochemistry in normal rats and in Brattleboro rats deficient in vasopressin and a neurophysin.

The cellular distribution of neurophysin was examined in hypothalami and neural lobes of normal Long-Evans rats and Brattleboro rats deficient in vasopressin and a major neurophysin. Tissue sections were treated with antisera to bovine, human, and rat neurophysins, using immunoperoxidase bridge techniques. Antisera to oxytocin (OT) and vasopressin (VP) were applied to adjacent sections. Two distinct cell populations were discernible in both magnocellular nuclei on the basis of the intensity of cytoplasmic staining. About half of the magnocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of homozygous Brattleboro rats with diabetes insipidus (DI) were devoid of immunoreactive neurophysin, OT, and VP. These cells were presumably the defective counterparts of those neurons that produce VP and its associated neurophysin in normal and heterozygous Brattleboro rats. The cells in homozygous DI rats which were stained with immunoreaction products to NP and OT were more concentrated in the dorsal part of the SON and in the periphery of the PVN. Spatial segregation of different neurons was also seen in the neural lobe, where clusters of stained axons were surrounded by bundles of nerve fibers lacking immunoreactive material. In normal rats and heterozygotes nearly all magnocellular neurons reacted immunologically with antiserum to neurophysin but with different intensities, so that "dark" and "light" cells could be distinguished. The darker cells in heterozygous Brattleboro rats had the same pattern of distribution as cells which contained OT. In homozygous DI rats, only some of those cells which contained neurophysin and OT exhibited a positive reaction with antiserum to VP due to slight reactivity with OT. The results obtained in the homozygous Brattleboro rat would suggest that OT and VP and their associated neurophysins are produced in different neurons in both the SON and PVN. However, in normal rats and in heterozygous Brattleboro rats, VP appeared to be present in both OT-positive and OT-negative neurons suggesting that some cells may have the capacity to synthesize two hormones.

Neurotensin neurons in the rat hypothalamus: an immunocytochemical study.

Neurotensin was localized in the hypothalamic tissues of adult Sprague-Dawley rats by immunoperoxidase techniques. Visualization of perikarya was greatly enhanced by intraventricular administration of colchicine. Many perikarya containing neurotensin-like immunoreactivity were seen in the medial preoptic area, the periventricular hypothalamus, the parvocellular portion of the paraventricular nucleus, the arcuate nucleus, and the lateral hypothalamus in the perifornical area. There were moderate numbers of cell bodies in the ventral portion of the anterior hypothalamus, the dorsomedial nucleus, and the posterior hypothalamus. No positive cells were seen in the suprachiasmatic, ventromedial, or mammillary nuclei. Reactive fibers were generally distributed in the same regions as cell bodies. Additional dense collections were seen in the lateral part of the zona externa of the median eminence, the pituitary stalk, the posterior mammillary nucleus, and the most lateral portions of the hypothalamus at the medial edge of the crura cerbri. There were smaller numbers of fibers found in the pre-mammillary and posterior hypothalamic nuclei and the posterior pituitary gland. These results indicate that the neurotensin system in the hypothalamus is very extensive and complex, as it is in many other brain regions. Neurons and fibers are found in many hypothalamic areas, including projections to the hypophysial portal system in the median eminence, suggesting that neurotensin may affect neuroendocrine mechanisms at several levels, including the anterior pituitary gland.

Intracellular localization of prolactin receptor and prolactin in the rat ovary by immunocytochemistry.

The localization of the PRL receptor as well as of PRL has been studied by immunoperoxidase techniques in the ovaries of cycling, pregnant, and lactating rats. Specific antisera to the receptor and to the hormone were used. By light microscopy, immunostaining for the PRL receptor coincided with that for the hormone. Staining was found intracellularly in most components of the ovary, except the theca, and was most striking in the luteal cells. Both PRL and its receptor were concentrated heavily in the ovum. Beginning 24-36 h postpartum, there was a change in the pattern of luteal cell staining, with a shift in the intensity of staining products to the periphery of the luteal cell, giving a ring appearance to these cells. The results suggest roles for PRL in ovarian function involving both maintenance of the corpus luteum and maturation of the ovum. This study also demonstrates the intracellular localization of a polypeptide hormone in association with its specific receptor.

Preoptic area brain grafts in hypogonadal (hpg) female mice abolish effects of congenital hypothalamic gonadotropin-releasing hormone (GnRH) deficiency.

Normal fetal preoptic area (POA), a site of GnRH production, was implanted into the third ventricle of adult female hypogonadal (hpg) mice. When the grafts were successful, the mice (genetically deficient in hypothalamic GnRH) responded with vaginal opening, cornified vaginal cells, ovarian and uterine development, and increased pituitary FSH content and plasma LH concentrations. Similar results were obtained with fetal POA tissue, whether derived from males or females. Two of four hpg mice with POA grafts mated when caged overnight with males. Hpg females that received cortical tissue from fetuses or from 16-day-old pups, or POA tissue from 16-day-old pups, showed none of these changes, remaining similar to untreated hpg females.

Control of release of adrenocorticotropin and vasopressin by the supraoptic and paraventricular nuclei.

To determine the relative roles of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei in the control of the release of vasopressin and of ACTH, we have examined the hormonal responses to electrical stimulation (200 microA, 0.2 msec, 100 Hz, 20 sec) of these regions. Cats were anesthetized with chloralose-urethane. Blood samples were taken 30 sec before stimulation and 1.5 min poststimulation. ACTH and vasopressin were measured by RIA. Electrical stimulation of the caudal pole of the SON increased vasopressin in plasma (1.82 +/- 0.41 microU/ml, n = 17, P less than 0.01) and decreased ACTH (-26 +/- 4 pg/ml, n = 13, P less than 0.01). In contrast, stimulation of the PVN increased vasopressin (2.01 +/- 0.60 microU/ml, n = 7, P less than 0.001) and increased ACTH (107 +/- 20 pg/ml, n = 32, P less than 0.01). Previous work has shown that vasopressinergic neurons of PVN, but not of SON, project to the zona externa of the median eminence. Other have suggested that the retrograde flow of blood from the neural lobe to the median eminence and thence to the anterior lobe would allow vasopressin to influence the release of ACTH. The present results indicate that both SON and PVN facilitate the release of vasopressin. However, PVN facilitates, but SON inhibits the release of ACTH. These findings suggest that the projection from PVN to the zona externa of the median eminence mediates the release of ACTH and that retrograde flow from the neural lobe is not important in the control of ACTH release during modest and transient increases in the release of vasopressin.

The hypothalamic magnocellular system of the rhesus monkey: an immunocytochemical study.

The hypothalamic magnocellular system of the adult female rhesus monkey is studied here, using immunoperoxidase technique and antisera to estrogen stimulated neurophysin (ESN), nicotine stimulated neurophysin (NSN), oxytocin (OT) and vasopressin (VP). These observations confirm and enlarge previous descriptions by others using Gomori techniques. It is apparent from this study that the magnocellular system spreads through a broader area than is generally accepted. A group of cells ventral to the head of the caudate nucleus and medial to the internal capsule is described. The general orientation of the nuclei and their tracts can only be appreciated when coronal, horizontal and sagittal sections are compared. Our observations suggest that the supraoptic nucleus is made up of a single group of cells that straddles the optic pathways, and is not divided in three segments, as it is generally described. It is also shown that the rostral extensions of the paraventricular and supraoptic nuclei merge above the optic chiasm. Cells containing ESN/OT and NSN/VP are evenly dispersed in the paraventricular nucleus but a topographical arrangement is present in the supraoptic nucleus. The magnocellular nuclei project to the organum vasculosum of the lamina terminalis, zona externa of the median eminence and pars nervosa of the pituitary gland. Reactive fibers were also seen within islets of cells from the pars intermedia located inside the pars nervosa. A globular structure containing small blood vessels surrounded by positive fibers was noticed protruding into the floor of the third ventricle, at the level of the median eminence.