The hypothalamic neuropeptide oxytocin is required for formation of the neurovascular interface of the pituitary.

The hypothalamo-neurohypophyseal system (HNS) is the neurovascular structure through which the hypothalamic neuropeptides oxytocin and arginine-vasopressin exit the brain into the bloodstream, where they go on to affect peripheral physiology. Here, we investigate the molecular cues that regulate the neurovascular contact between hypothalamic axons and neurohypophyseal capillaries of the zebrafish. We developed a transgenic system in which both hypothalamic axons and neurohypophyseal vasculature can be analyzed in vivo. We identified the cellular organization of the zebrafish HNS as well as the dynamic processes that contribute to formation of the HNS neurovascular interface. We show that formation of this interface is regulated during development by local release of oxytocin, which affects endothelial morphogenesis. This cell communication process is essential for the establishment of a tight axovasal interface between the neurons and blood vessels of the HNS. We present a unique example of axons affecting endothelial morphogenesis through secretion of a neuropeptide.

Brain-endocrine interactions: a microvascular route in the mediobasal hypothalamus.

Blood-borne hormones acting in the mediobasal hypothalamus, like those controlling food intake, require relatively direct access to target chemosensory neurons of the arcuate nucleus (ARC). An anatomical substrate for this is a permeable microvasculature with fenestrated endothelial cells in the ARC, a system that has awaited comprehensive documentation. Here, the immunofluorescent detection of endothelial fenestral diaphragms in the rat ARC allowed us to quantitate permeable microvessels throughout its rostrocaudal extent. We have determined that permeable microvessels are part of the subependymal plexus irrigating exclusively the ventromedial (vm) ARC from the subadjacent neuroendocrine median eminence. Unexpectedly, permeable microvessels were concentrated proximal to the pituitary stalk. This marked topography strongly supports the functional importance of retrograde blood flow from the pituitary to the vmARC, therefore making a functional relationship between peripheral long-loop, pituitary short-loop, and neuroendocrine ultra-short loop feedback, altogether converging for integration in the vmARC (formerly known as the hypophysiotrophic area), thereby so pivotal as a multicompetent brain endocrinostat.

Neuroimaging in posttraumatic hypopituitarism.

Posttraumatic hypopituitarism is the failure of the hypothalamic-pituitary axis secondary to traumatic brain injury. It can clinically present as decreased muscle mass, concentration, libido, and fertility. It can also present as increased fatigue, depression, and cognitive deficits. In addition, electrolyte abnormalities such as hyponatremia can occur in hypopituitarism. As a result of heightened awareness of posttraumatic hypopituitarism, it is a phenomenon that is becoming more commonly diagnosed. Posttraumatic hypopituitarism is a diagnosis based on clinical evaluation, laboratory testing, and neuroimaging. Of the radiological techniques, magnetic resonance imaging is the preferred technique to image the pituitary gland. This article contains coronal and sagittal magnetic resonance imaging of the posterior fossa, illustrating the normal hypothalamus and pituitary gland as well as adjacent structures. The sequential enhancement pattern of the normal pituitary gland is consistent with its vascular supply. A colored illustration was created to display the vascular supply to the hypothalamus, pituitary stalk, and pituitary gland.

Glutamatergic innervation of the hypothalamic median eminence and posterior pituitary of the rat.

Recent studies have localized the glutamatergic cell marker type-2 vesicular glutamate transporter (VGLUT2) to distinct peptidergic neurosecretory systems that regulate hypophysial functions in rats. The present studies were aimed to map the neuronal sources of VGLUT2 in the median eminence and the posterior pituitary, the main terminal fields of hypothalamic neurosecretory neurons. Neurons innervating these regions were identified by the uptake of the retrograde tract-tracer Fluoro-Gold (FG) from the systemic circulation, whereas glutamatergic perikarya of the hypothalamus were visualized via the radioisotopic in situ hybridization detection of VGLUT2 mRNA. The results of dual-labeling studies established that the majority of neurons accumulating FG and also expressing VGLUT2 mRNA were located within the paraventricular, periventricular and supraoptic nuclei and around the organum vasculosum of the lamina terminalis and the preoptic area. In contrast, only few FG-accumulating cells exhibited VGLUT2 mRNA signal in the arcuate nucleus. Dual-label immunofluorescent studies of the median eminence and posterior pituitary to determine the subcellular location of VGLUT2, revealed the association of VGLUT2 immunoreactivity with SV2 protein, a marker for small clear vesicles in neurosecretory endings. Electron microscopic studies using pre-embedding colloidal gold labeling confirmed the localization of VGLUT2 in small clear synaptic vesicles. These data suggest that neurosecretory neurons located mainly within the paraventricular, anterior periventricular and supraoptic nuclei and around the organum vasculosum of the lamina terminalis and the preoptic area secrete glutamate into the fenestrated vessels of the median eminence and posterior pituitary. The functional aspects of the putative neuropeptide/glutamate co-release from neuroendocrine terminals remain to be elucidated.

17beta-estradiol differentially regulates blood-brain barrier permeability in young and aging female rats.

Because both brain and its vasculature are potent targets of estrogen, age-related decline in estrogen levels or alterations in estrogen receptors may disrupt the integrity of the blood-brain barrier, leading to increased influx of toxic products. The present study tested the hypothesis that the blood-brain barrier is more permeable in reproductive senescent animals and will respond differently to estrogen replacement as compared with young adult females. Young adult and reproductive senescent rats were ovariectomized and replaced with an estrogen or control pellet. We found a 2- to 4-fold increase in extravasation of dye in the olfactory bulb and hippocampus of reproductive senescent females compared with young adults. Furthermore, estrogen significantly reduced dye extravasation in both olfactory bulb and hippocampus in young adults compared with age-matched counterparts that received a control pellet. However, estrogen replacement increased dye extravasation in the hippocampus of reproductive senescent females compared with age-matched control-pellet replaced animals, whereas dye extravasation was unchanged by estrogen in the olfactory bulb of senescent females. There were no age- and estrogen-related differences in dye accumulation in the pituitary gland, which is a circumventricular organ. These results support the hypothesis that the hormonal decline that marks reproductive senescence leads to increased permeability of the blood-brain barrier, which is further exacerbated by estrogen treatment in specific regions.

[Hypothalamic glial cells and endothelial cells as key regulators of GnRH secretion]. / Des acteurs clés de la régulation de la sécrétion de GnRH: les cellules gliales et endothéliales de l'hypothalamus.

During the last decade, compelling evidence has been provided that, in addition of being regulated by transsynaptic inputs, GnRH neuroendocrine secretion is modulated by factors released both by glial cells and the endothelium of pituitary portal blood vessels. Glial cells exert their regulatory influence on GnRH release through the secretion of growth factors, such as TGFbetas and peptides member of the EGF family, that act either directly on GnRH neurons or require prostaglandin release from astrocytes, respectively. On the other hand vascular endothelial cells stimulate GnRH release via NO secretion. In addition, recent studies suggest that both glial cells and endothelial cells of the median eminence can modulate the direct access of GnRH neuroendocrine terminals to the vascular wall and thus control GnRH release efficiency. During the reproductive cycle, direct neurovascular contacts of GnRH nerve endings, that are engulfed in tanycytic endfeet, only occur at periods when massive GnRH release is required, i.e., at the onset of the preovulatory GnRH/LH surge on the day of proestrus. Recent in vitro and in vivo data demonstrate that both glial (TGFalpha and TGFbeta) and endothelial (NO) factors can induce such morphological plasticity. Neuro-glio-endothelial interactions at the median eminence of the hypothalamus thus appear to be key regulatory mechanisms for GnRH neuroendocrine secretion.

Does cortisol inhibit pulsatile luteinizing hormone secretion at the hypothalamic or pituitary level?

Elevations in glucocorticoids suppress pulsatile LH secretion in sheep, but the neuroendocrine sites and mechanisms of this disruption remain unclear. Here, we conducted two experiments in ovariectomized ewes to determine whether an acute increase in plasma cortisol inhibits pulsatile LH secretion by suppressing GnRH release into pituitary portal blood or by inhibiting pituitary responsiveness to GnRH. First, we sampled pituitary portal and peripheral blood after administration of cortisol to mimic the elevation stimulated by an immune/inflammatory stress. Within 1 h, cortisol inhibited LH pulse amplitude. LH pulse frequency, however, was unaffected. In contrast, cortisol did not suppress either parameter of GnRH secretion. Next, we assessed the effect of cortisol on pituitary responsiveness to exogenous GnRH pulses of fixed amplitude, duration, and frequency. Hourly pulses of GnRH were delivered to ewes in which endogenous GnRH secretion was blocked by estradiol. Cortisol, again, rapidly and robustly suppressed the amplitude of GnRH-induced LH pulses. We conclude that, in the ovariectomized ewe, cortisol suppresses pulsatile LH secretion by inhibiting pituitary responsiveness to GnRH rather than by suppressing hypothalamic GnRH release.

L1 and laminin: their expression during rat hypophysis ontogenesis and in adult neurohemal areas.

L1 is a murine multidomain glycoprotein implicated in cell aggregation, fasciculation. neurite outgrowth and synaptogenesis. Laminin, a trimeric polypeptide, is implicated in neuronal survival, growth cone guidance, neurite outgrowth and cell differentiation. Laminin can also interact with the cell adhesion molecule L1. Their expressions were investigated from embryonic day 15 (E15) to adult in the rat hypophysis, and in adult neurohemal zones. Detected in the neural lobe from E17, the L1 immunoreactivity increased during prenatal development and persisted in adulthood mainly related to the neuropeptidergic fibers. Pituicytes were only labelled on the plasmalemma apposed to axons. In the intermediate lobe, L1 appeared at birth on folliculo-stellate cells extensions, constituting a network which densified during postnatal development. L1 is also expressed in all neurohemal areas on neuronal profiles. Laminin was clearly detectable in the hypophysis at E15 before the first blood vessels penetrate the Rathke pouch. At E20, all the basal membranes of the blood vessels were stained. In the intermediate lobe, a spotted laminin immunoreactivity was detected at E21. At this stage, we observed the staining of intercellular spaces and the intracellular labelling of melanotrophs, concerning reticulum or vesicles. The staining of melanotrophs seemed to maintain during adulthood. In contrast with blood vessels of the adult cerebral tissue, adult capillaries of the neural lobe and the others neuro-hemal zones were intensely labelled with the anti-laminin antibody. These results suggest that neurite outgrowth and neurite guidance could be promoted by L1 and laminin in the neurointermediate lobe. The "intercellular tunnels" could also be an important guidance cue for migrating cells in the intermediate lobe. These data also demonstrate that melanotrophic cells. secreting the laminin, have a role in the ontogenesis of the gland. Finally, we suggest that L1 and laminin can collaborate to reinforce "neurons-capillaries" interactions in neurohemal zones.

Does a short loop feedback mechanism for the control of luteinizing hormone secretion exist in the ewe?

It is not known whether a short loop feedback mechanism for the regulation of LH exists in sheep. This study on ovariectomized ewes investigated whether a bolus injection (10, 1, and 0.1 microg LH or 1 microg BSA; n 4) or a 3-h continuous infusion of exogenous LH (100 or 1 ng/min; n = 7) into the third ventricle through a permanent indwelling cannula could influence the activity of the GnRH pulse generator, as determined by measurement of endogenous LH secretion. To assess the potential for involvement in a LH short loop feedback system and to estimate the level of LH in the hypothalamic milieu, the concentrations of LH in the peripheral circulation, portal circulation, and third ventricle were measured during an estradiol-induced preovulatory LH surge (n = 4). Neither the bolus nor continuous administration of LH into the third ventricle had any effect on the mean interpulse interval, nadir, pulse amplitude, or circulating level of systemic LH. Furthermore, despite portal LH concentrations being more than 20-fold higher than jugular LH concentrations, LH levels in third ventricular cerebrospinal fluid remained barely detectable and did not reflect dynamic secretory events in the peripheral or hypothalamo-hypophyseal portal blood. These data demonstrate that in ewes, little pituitary LH reaches the third ventricle, and the small amount that does is unable to affect peripheral gonadotropin release. Our study suggests, therefore, that a short loop feedback system for LH does not exist in the ewe.

Macroscopic blood supply to the hypophysis and hypothalamus of the ostrich (Struthio camelus).

The branching pattern of the Aa. carotes internae and the macroscopic blood supply to the hypophysis and hypothalamus of the ostrich were studied on ten dissected acrylic vascular-injected heads and ten corrosion preparations of acrylic vascular casts of the head. The A. carotis cerebralis was found to be the only source of blood supply to the hypophysis and hypothalamus. The neurohypophysis was supplied by the caudal hypophyseal and infundibular arteries. The pars distalis was supplied by portal vessels from the ventral hypothalamic region, and it also received arterial blood directly from the infundibular arteries. The hypothalamus received blood from the Aa. infundibulares. A. ventralis tecti mesencephali and A. preopticae.

Dynamics of the regulation of the hypothalamo-pituitary-adrenal (HPA) axis determined using a nonsurgical method for collecting pituitary venous blood from horses.

Since 1985, we have applied our nonsurgical technique for collecting pituitary venous (PitVen) blood from ambulatory horses to investigate the regulation of adrenocorticotropic hormone (ACTH) secretion. This method offers particular advantages for studying the hypothalamo-pituitary-adrenal axis since its benign nature enables hypothalamic and pituitary interactions to be monitored without disturbing the animal, and the horse's large blood volume allows 3- to 4-ml samples to be collected as frequently as every 20s for prolonged periods so that the secretion patterns of ACTH and its secretagogues can be precisely defined. When PitVen blood was sampled every 20 or 30s during the circadian maximum, arginine vasopressin (AVP) and ACTH secretion patterns were complex and irregular, with mean interpeak intervals of approximately 5 min. Despite their erratic patterns, AVP and ACTH secretions were closely coupled on cross-correlation analysis. By contrast, PitVen corticotropin-releasing hormone (CRH) concentrations were low, relatively stable, and not consistently related to ACTH secretion. However, when cortisol negative feedback was reduced acutely by metyrapone infusion, CRH and AVP secretion were stimulated. Mathematical modeling suggested that CRH had become the more effective secretagogue and that much of the ACTH response was mediated by increased pituitary responsiveness to CRH. Elevated blood osmolality triggered synchronous AVP and ACTH secretion, without altering PitVen CRH. In this case, the source of PitVen AVP was presumably the magnocellular/neurohypophysial pathway, which is thought to respond primarily to changes in blood osmolality and pressure. Our results suggest that this pathway also participates in ACTH regulation. We have studied the effect of several perturbations and found, as have others, that the secretagogues released vary with the stimulus given. For example, vigorous exercise promptly raised PitVen AVP and ACTH, but not PitVen CRH. Hypoglycemia provoked both CRH and AVP secretions, with the CRH increment being inversely proportional to the glucose nadir. Administration of the opioid antagonist, naloxone, increased PitVen ACTH; however, changes in AVP and CRH were variable and overall could not account for the ACTH response. This suggests that endogenous opioids inhibit a third ACTH secretagogue, stimulate an inhibitory factor, or also act at the pituitary. Chronic social stress, induced by confining newcomers with aggressive, resident mares, caused most introduced horses to become submissive. In such horses, plasma cortisol declined to levels similar to those during metyrapone infusion. Despite hypocortisolemia, PitVen ACTH was low, whereas PitVen CRH tended to be elevated. Moreover, chronically stressed horses did not respond to exogenous CRH. We conclude that at rest and during some perturbations AVP is the immediate stimulus for ACTH release. Even ACTH micropulses, previously thought to occur spontaneously, appear to be regulated by AVP in horses. On the other hand, CRH secretion and pituitary responsiveness to CRH rise when cortisol falls, suggesting that a major role for CRH is to fix the cortisol setpoint. However, during chronic stress, these relationships become disturbed, with results to date pointing toward the existence of an ACTH-release inhibiting factor.

[Topography of the hypophysis and its neighboring structures]. / Topographie der Hypophyse und der benachbarten Strukturen.

The first part of the article informs about four points: the skeletal structures of the middle cranial fossa, the basic divisions of the gland and their connections with the hypothalamus, its blood supply, and its development. The topographic part deals with the incorporation of the pituitary gland in the sella turcica, its relationship to the meninges, the subarachnoid cavity and other neighbouring structures, especially the sphenoidal sinus, the posterior ethmoidal cells as well as the chiasma opticum. With respect to the latter, the position of the fibres in the optic nerve, chiasma and optic tract and the consequences of lesions in characteristic areas are described. Finally, the variant structures of the cavernous sinus and the topography of its contents are discussed. Detailed data can be found about the course of the oculomotor nerves and the possible locations of their lesions.

Varied microcirculation of pituitary adenomas at rapid, dynamic, contrast-enhanced MR imaging.

PURPOSE: Rapid, dynamic, contrast material-enhanced magnetic resonance imaging was performed to evaluate the early enhancement patterns of normal pituitary structures, macroadenomas, and microadenomas. MATERIALS AND METHODS: A 1.5-T imager with a circularly polarized head coil was used on 40 patients referred for investigation of endocrinopathy, of neurologic deficit, or for follow-up of a previously documented pituitary tumor. RESULTS: The technique provided a temporal resolution of one image per 1.25 seconds, allowing discrimination of primary arterial and secondary portal circulation enhancement phases of pituitary structures and tumors. Arterial-phase enhancement of 16 macroadenomas was observed, suggesting a primary arterial blood supply to these lesions. Five microadenomas showed minimal enhancement in the secondary portal circulation phase. A brief temporal phase was also captured, in which cavernous sinus invasion by tumor was visualized as a "filling defect" within the gadolinium-laden laterosellar venous spaces. CONCLUSION: The technique reveals the microcirculatory dynamics associated with pituitary adenomas and suggests a dominant arterial blood supply for macroadenomas. It can supplement routine spin-echo imaging for determination of cavernous sinus invasion. Limitations related to section positioning, resolution, and signal-to-noise ratio exist.

Microcirculatory patterns in adult rat cerebral hypophysis: a scanning electron microscope study of replicated specimens.

The blood vascular bed of the cerebral hypophysis in the adult rat was replicated completely or incompletely by arterial injection of different amounts of methacrylate resin, to be observed with a scanning electron microscope. Complete replication confirmed our previous findings (Murakami et al., 1987) on the distribution and structure of the vascular beds in and around the hypophysis of the rat. One long major and several minor portal routes (vide infra) were reproduced sufficiently together with the systemic veins of the posterior lobe. Incomplete replication demonstrated that resin flows: 1) via the long portal vessels from the median eminence and neural stalk to the anterior lobe; 2) via the accessory long portal vessels from the subependyma to the anterior lobe; 3) via the short portal vessels from the posterior lobe to the anterior lobe; 4) via the neuro-intermedial portal vessels from the posterior lobe to the intermediate lobe; 5) via the intermedio-distal portal vessels from the intermediate lobe to the anterior lobe; and 6) via the tuberal portal vessels from the tuberal lobe to the anterior lobe. Incomplete replication also demonstrated that resin in the median eminence and neural stalk is drained preferentially into the anterior lobe via the long portal vessels, and that resin in the posterior lobe is drained mainly into the systemic veins. We were unable to demonstrate a retrograde resin flow from the anterior lobe to the median eminence, subependyma, neural stalk, intermediate lobe and posterior lobe, nor an ascending resin flow from the posterior lobe to the median eminence and subependyma. Also failing to be noted were an ascending resin flow from the hypophysis to the hypothalamus and a descending resin flow from hypothalamus to the hypophysis.

Passive immunization and hypothalamic peptide secretion.

Passive immunization is a common approach used to eliminate the biological activity of an endogenous substance by its binding to a specific antibody (Ab). Surprisingly little information has been gathered on the mechanisms involved. Moreover, the possibility that immunoneutralization could affect also the secretion of the antigen itself has been mostly ignored. To study hypothalamic neuropeptide secretion under the condition of passive immunization, labeled and unlabeled monoclonal antibody (MoAb) against arginine vasopressin (AVP) was injected intravenously. After 2 h a similar amount of 125I-MoAb was found in hypophyseal portal and peripheral (femoral artery) plasma, showing a distribution volume of 73.2 ml/kg. Assessment of the MoAb dilution in the same plasma samples from the binding studies revealed substantially higher dilutions (800-5,700 ml/kg). Such a MoAb dilution (saturation) would be attained by the binding of 130-290 pmol AVP/ml plasma. The calculated amount of plasma AVP decreased by one half within the interval from 2 to 24 h after Ab injection, similarly as did the 125I-MoAb content. Intravenous injection of polyclonal corticotropin-releasing hormone (CRH) Ab resulted in a decrease of plasma adrenocorticotropin and corticosterone levels. After 24 h the dilution of the Ab in portal plasma exceeded two times that in peripheral plasma. CRH concentrations of 0.6-2.5 pmol/ml were found by specific radioimmunoassay after its dissociation from the Ab in plasma. The CRH concentration was higher in portal than in peripheral plasma and was related to the amount of the Ab injected. CRH mRNA levels in the paraventricular nucleus were significantly increased in CRH Ab as compared with normal rabbit serum injected rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of starvation and subsequent refeeding on thyroid function and release of hypothalamic thyrotropin-releasing hormone.

Effects of starvation on thyroid function were studied in 5- to 6-week-old (R x U) F1 rats. Starvation lowered plasma TSH in female, but not in male rats. Plasma T4 and T3 levels decreased, whereas the dialysable T4 fraction increased during starvation. Free T4 (FT4) levels decreased rapidly in females, but only after prolonged fasting in male rats. Glucose decreased, and free fatty acid levels increased during starvation. Peripheral TRH levels did not change during food deprivation. Since effects of starvation were most apparent in young female rats, such rats were used to study hypothalamic TRH release during starvation and subsequent refeeding. Basal in vitro hypothalamic TRH secretion was less in starved rats than in control or refed animals. In vitro hypothalamic TRH release in medium with 56 mM KCl increased 3-fold compared to basal release, and in these depolarization conditions TRH release was similar between hypothalami from control, starved and refed rats. In rats starved for 2 days, TRH level in hypophysial portal blood was lower than that of controls. Thus, diminished thyroid function during starvation may at least in part be caused by a reduced hypothalamic TRH release.

Tetrapod-like hypothalamo-hypophysial portal system in the teleost Megalops cyprinoides (Broussonet).

A tetrapod-like hypothalamo-hypophysial portal system and a persistent bucco-hypophysial canal are present in Megalops cyprinoides. The complicated loops of the primary capillary plexus are seen on the ventral side of the infundibular floor and contact the perikarya of the nucleus lateralis tuberis and the preoptico-hypothalamo-neurohypophysial-neurosecretory tract. Although the pars intermedia receives part of its vascular supply from the pars distalis, the caudal hypophysial artery directly vascularizes the neurointermedia interface and forms the plexus intermedialis. The bucco-hypophysial canal is short and narrow in the fry and fingerlings but becomes long and tortuous as the fish grows. Megapopidae seem to be closer to the polypteriformids than to the teleosts. The possession of the pituitary portal system in megalopids may be a connecting link between the polypteriformids and other advanced teleosts.

Dopa accumulates in the hypothalamic-hypophysial portal vessels and is taken into the anterior pituitary of NSD-1015-treated rodents.

DOPA was measured in the anterior pituitary and hypothalamic-hypophysial portal blood after treatment with NSD-1015, a DOPA decarboxylase inhibitor. NSD-1015 caused DOPA to accumulate in the anterior pituitary of mice and rats, and increased DOPA in the hypothalamic-hypophysial portal blood of rat. Serum prolactin was also increased. Interruption of the anterior pituitary blood supply from the hypothalamic-hypophysial system by cannulation of the entire pituitary stalk eliminated the NSD-1015-induced DOPA accumulation in the rat pituitary. We conclude that DOPA can be taken into the anterior pituitary from the portal blood of NSD-1015-treated rodents and that the anterior pituitary lacks tyrosine hydroxylase activity in both mice and rats.

Hypothalamopituitary deficiency and precocious puberty following hyperhydration in diabetic ketoacidosis.

We report on a 5-year-old child who survived an intracerebral crisis, following ketoacidosis-revealing diabetes (DKA), with visual impairment due to a vascular occipital lesion. Two and 4 months after the initial episode, a unique hypothalamopituitary disorder consisting in GH, ACTH, TSH deficiencies and central precocious puberty, was detected. Cranial magnetic resonance images showed no visible lesion in the hypothalamopituitary region. The most likely hypothesis is the ischemia of hypothalamopituitary and occipital regions following possible cerebral edema after hyperhydration. She survived with low visual acuteness and received a combined replacement therapy for the neuroendocrinological deficiencies. This case emphasizes that the rehydration at the initial period of DKA is critical, especially when risk factors for cerebral edema are present (young age, marked hyponatremia). The neuroendocrinological consequences of acute cerebral edema are rare, but physicians must be attentive in survivors of these accidents.

Hypothalamic corticotropin-releasing hormone (CRH) secretion into hypophysial portal blood is regulated by cutaneous sensory stimulation in anesthetized rats.

The effects of noxious and non-noxious mechanical stimulation of various segmental skin areas (face, forelimb and forepaw, abdomen, hindlimb and hindpaw) on the secretion of immunoreactive corticotropin-releasing hormone (iCRH) from the hypothalamus into hypophysial portal blood was examined in artificially ventilated rats under halothane anesthesia. Secretion of iCRH was calculated from the iCRH concentration in hypophysial portal plasma and the plasma flow rate. Noxious mechanical stimulation of the skin was delivered by pinching using surgical clamps, while non-noxious mechanical stimulation was provided by brushing with tooth brushes. Pinching of the bilateral forepaws or hindpaws and brushing of the bilateral hindlimbs for 20 min increased hypothalamic iCRH secretion. In contrast, pinching of the face or abdomen and brushing of the face, forelimbs, or abdomen for 20 min did not significantly influence it. These results indicate that cutaneous mechanical sensory stimulation contributes to the reflex regulation of CRH secretion from the hypothalamus into hypophysial portal blood, and also that this effect is highly dependent on the site of stimulation.