The circumventricular organs: an atlas of comparative anatomy and vascularization.

The circumventricular organs are small sized structures lining the cavity of the third ventricle (neurohypophysis, vascular organ of the lamina terminalis, subfornical organ, pineal gland and subcommissural organ) and of the fourth ventricle (area postrema). Their particular location in relation to the ventricular cavities is to be noted: the subfornical organ, the subcommissural organ and the area postrema are situated at the confluence between ventricles while the neurohypophysis, the vascular organ of the lamina terminalis and the pineal gland line ventricular recesses. The main object of this work is to study the specific characteristics of the vascular architecture of these organs: their capillaries have a wall devoid of blood-brain barrier, as opposed to central capillaries. This particular arrangement allows direct exchange between the blood and the nervous tissue of these organs. This work is based on a unique set of histological preparations from 12 species of mammals and 5 species of birds, and is taking the form of an atlas.

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.

Dynamic MRI in the congenital agenesis of the neural pituitary stalk syndrome: the role of the vascular pituitary stalk in predicting residual anterior pituitary function.

OBJECTIVE: Magnetic resonance imaging (MRI) without contrast medium is unable to give detailed information on the hypothalamic-pituitary structures. MRI using gadopentetate dimeglumine (Gd-DTPA), and dynamic MRI, were performed in patients with hypopituitarism previously diagnosed as having anterior pituitary hypoplasia, ectopic posterior pituitary and unidentified pituitary stalk (1) to determine whether Gd-DTPA improves the delineation of hypothalamic-pituitary structures; (2) to verify whether, if so, such improvement can be correlated with residual pituitary function in patients subjected to long-term follow-up; and (3) to identify the hypothalamic-pituitary vascular network in such cases. PATIENTS: Eighteen patients (13 males, 5 females) aged 10-26.4 years with unidentified pituitary stalk at first MRI study were evaluated. Eight had isolated GH deficiency (IGHD), and 10 had multiple pituitary hormone defect (MPHD) with the progression to complete anterior pituitary deficits seen by the age of 15 years in 8 patients (1 had GH and FSH-LH deficiency and 1 had GH, TSH and FSH-LH deficiency). RESULTS: The MRI revealed a very thin pituitary stalk in 7 patients (38.8%), 6 with IGHD (75%) and 1 (10%) with MPHD (GH and FSH-LH deficiency), after Gd-DTPA administration. Reassessment of anterior pituitary function showed that the thyroid, adrenal and gonadal functions were intact in the 6 patients with IGHD and pituitary stalk identified by Gd-DTPA as well as in one IGHD patient with no evidence of pituitary stalk. In one 10-year-old with IGHD at the time of presentation (6 years) and no pituitary stalk seen after Gd-DTPA, subclinical hypothalamic hypothyroidism and suspected hypogonadotropic hypogonadism were documented. Partial ACTH deficiency was recorded in the patient with TSH and FSH-LH deficiency with no pituitary stalk. After Gd-DTPA, patients with absent pituitary stalk had a risk of developing MPHD 27 times greater than had those with an identified pituitary stalk (relative risk = 27, 95% confidence interval 1.9-368.4, Fisher's exact test P = 0.009). Dynamic MR images obtained every 4.6 s revealed rapid enhancement of hypothalamic-pituitary structures and allowed the determination of the times to initial enhancement of ectopic posterior pituitary and hypoplastic anterior pituitary which ranged between 9.2 and 18.4 s, and that of complete anterior pituitary (32.2-41.4 s). The time to maximum enhancement of anterior pituitary was significantly longer than in controls (35.5 +/- 3.8 s vs 25.2 +/- 1.6 s, P < 0.0001). CONCLUSIONS: MRI with Gd-DTPA proved more sensitive in identifying the vascular component of pituitary stalk and added new information about the partial preservation of hypothalamo-hypophyseal portal vessels. The vascular pituitary stalk is easily recognized after Gd-DTPA in most IGHD patients, but exceptionally in MPHD; this sheds light on the possible normal course of affected patients. The neural component of the pituitary stalk is lacking regardless of whether patients have IGHD or MPHD, indicating that the term congenital agenesis of the neural pituitary stalk is more appropriate than pituitary stalk interruption. The times to enhancement of ectopic posterior pituitary and residual anterior pituitary obtained by the fast-framing MRI technique disclose dynamic changes in regional blood supply which appear direct, arterial and mainly independent of the portal system.

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.

An in situ study of the hypothalamo-neurohypophysial complex of the freshwater teleost Ompok bimaculatus (Bloch) with a note on the tetrapodan features of its vascularization.

In Ompok bimaculatus the neurosecretory axons of both the pars magnocellularis and pars parvocellularis component of the nucleus preopticus contribute to the formation of the left and right main tracts. At rostral levels, one third of the tracts are loosely built forming a king of curtain, while they become more compact at caudal levels. The caudal two thirds of the main tracts give off several pairs of lateral tracts which join at the midline to form the paired median tracts. The median and the main tract jointly enter the pituitary as a common tract which, on entering the proximal pars distalis, separates into two and enters the pars intermedia. The hypothalamic and the hypophysial arteries take their origin from the internal carotid artery. The former contribute to the formation of the primary capillary plexus of the median eminence, whereas the latter enter the pituitary directly and ramify in the neuroadeno-interface. The primary capillary plexus is in close topographical contact with the neurosecretory axonal complex where the median and common tracts are formed. At this site at least some axons might have their endings on the capillary plexus. Thus, this region my be comparable in structure to the median eminence of the tetrapods. The neurons of the nucleus lateralis tuberis of O. bimaculatus are AF-positive. The infundibular cavity extends into the main neurohypophysial trunk and is lined by ependymal cells like the third ventricle.

The hypothalamo-neurohypophysial system in Indian fresh-water goby, Glossogobius giuris (Ham.).

The hypothalamo-neurohypophysial neurosecretory system in Indian fresh-water goby, Glossogobius giuris (Ham.) has been described. The tractus preoptico-hypophyseus serves the function of a morphological and physiological connection between the hypothalamus and pituitary gland. In addition to main mass of the nucleus preopticus cells (cystine/cysteine bearing), a group of few cells in the hypothalamus has also been observed. These cells are situated posterior to the position of the nucleus preopricus and are CH Ph + ve and AF + ve. The neurosecretory material in the cells of nucleus preopticus is in the form of fine granules. The nucleus lateralis tuberis is absent in the fish under study. The disposition of neurosecretory material is heaviest along the fibres of the neurohypophysis in the region of pars intermedia with which it forms a profuse interdigitation. The fibres usually terminate over the blood vessels. The Herring bodies are noticeable at different levels in the neurohypophysis and pars-distalis. Besides the neurosecretory fibres, Herring bodies, non-stainableneurosecretory fibres and blood vessels, the pituicytes are also present in the neurohypophysis (SAKSENA 1974a, b). The intraaxonal flow of neurosecretory material, the vascularization of the nucleus preopticus and hypothalamo-hypophysial regulatory mechanism have been also discussed.

Can the pituitary secrete directly to the brain? (Affirmative anatomical evidence).

Vascular casts of 10 rhesus monkey pituitary glands and three vascular casts of the rhesus monkey cavernous sinus were examined by scanning electron microscopy. A continuous neurohypophyseal capillary bed was found uniting the infundibulum, infundibular stem, and infundibular process. The neurophypophysis was supplied by three groups of arteries: superior hypophyseal, middle hypophyseal, and inferior hypophyseal. Numerous anastomoses were found between individual arteries, and some hypophyseal arteries formed anastomotic links between different portions of the circle of Willis. Veins located at the caudal pole of the infundibular process, capillaries linking the infundibulum to the hypothalamus, and portal vessels extending from the infundibulum to the adenohypophysis provided efferent vascular pathways from the neurohypophysis. The adenohypophysis received no direct arterial supply; its entire afferent vascular supply was provided by portal vessels. Lateral hypophyseal veins were not found; small adenohypophyseal veins joined larger neurohypophyseal veins to form confluent pituitary veins which extended to the cavernous sinus. The capacity of the venous connections draining the adenohypophysis directly to the cavernous sinus appeared small when compared to that of of the long portal vessels supplying the adenohypophysis. However, many of the short portal vessels interposed between the adenohypophysis and the infundibular stem and process were well arranged to function as alternative efferent routes from the adenohypophysis. The limited potential for venous drainage directly to the cavernous sinus suggests that blood leaves the adenohypophysis by other routes; blood carried via long portal vessels from the infundibulum to the adenohypophysis may return to the neurohypophyseal capillary bed via short portal vessels. This anatomical study suggests that hypothalamic and adenohypophyseal secretions are conveyed to the capillary bed of the neurohypohysis. These secretions may leave the neurohypophysis via any of seven potential routes: one efferent route is directed to the adenohypophysis, another route is directed to the systemic circulation, but five of the potential efferent routes are directed toward the brain.

Relationship between luteinizing hormone releasing hormone concentration in hypophysial portal blood and luteinizing hormone release in intact, castrated, and electrochemically-stimulated rats.

The concentration of luteinizing hormone releasing hormone (LHRH) in hypophysial portal plasma was determined in pentobarbital anesthetized,intact and castrated rats of both sexes, including proestrous rats following electrochemical stimulation of the medial preoptic area (MPOA). Mean LHRH levels in portal plasma obtained between 1400--1700 h from estrous and diestrous rats and from rats ovariectomized for 8 weeks were similar and ranged from 50--55 pg/ml, but the LHRH levels in proestrous rats were less than 12 pg/ml. In addition, hypophysial portal plasma collected during 1100 to 1400 h from animals orchidectomized for 8 weeks and from intact male rats contained mean LHRH concentrations that ranged from 50--65 pg/ml and 30--35 pg/ml, respectively. Electrochemical stimulation of the MPOA in the female rat on the afternoon of proestrus resulted in a marked increase in the concentration of LHRH in portal plasma. LHRH levels in portal plasma during the 0 to 30, 30 to 60, 60 to 90, 90 to 120, and 120 to 150-min periods after electrochemical stimulation of the MPOA were 105 +/- 24.2, 61 +/- 10.8, 51 +/- 8.2, 36 +/- 5.3, and 32 +/- 4.1 pg/ml, respectively. LHRH levels in portal plasma from the unstimulated rats were not detectable (less than 12 pg/ml) in most of the animals. In another group of proestrous rats, the effect of rabbit anti-LHRH serum or normal rabbit serum (NRS) on the release of LH after electrochemical stimulation of MPOA was examined. Pretreatment of proestrous rats with anti-LHRH serum blocked the release of LH due to MPOA stimulation, whereas pretreatment with NRS did not inhibit LH release. On the basis of these findings, it is concluded that electro-chemical stimulation of the MPOA in proestrous rats increases LHRH levels in portal blood and that the enhanced secretion of LHRH stimulates the release of LH from the pituitary gland.

Water deprivation for 24 hours increases selectively blood flow in posterior pituitary of conscious rats.

Blood flow was measured by means of 125I-Antipyrin distribution and was found to be increased in the posterior pituitary of conscious rats following water deprivation for 24 h as compared to either normohydrated control or to force hydrated rats (2.86 ml min-1 g-1 vs. 2.36 ml or 2.08 ml, respectively). Other parameters of systemic haemodynamics, blood flow in the brain or in the hypothalamus and in anterior pituitary did not differ in three experimental groups of rats subjected to various water intake. The increased blood flow in the posterior pituitary in dehydrated rats presumably parallels the locally intensified metabolic rats due to the enchanged stimulation of the antidiuretic hormone release.

Scanning microscopy of pituitary vascular casts.

Vascular casts of the pituitary-median eminence complex from seventeen adult female rabbits were examined with the scanning electron microscope. The results of this study confirm the presence of a single capillary bed common to the entire neurohypophysis. Arterial supply to the rabbit pituitary is only to the neurohypophysis. A direct supply to adenohypophysis was not found. Within the median eminence there are an external and internal capillary plexus. The internal capillary plexus is directed toward the infundibular recess of the third ventricle. It does not receive a direct arterial supply but derives its blood supply from the external plexus before draining to the adenohypophysis. Vessels of the posterior median eminence are confluent with vessels of the infundibular stem. On the basis of these studies, it is proposed that the entire neurohypophysis, not simply the median eminence, serves as the final common pathway to the glandular pituitary. It is also proposed that in the median eminence, vessels are organized to deliver blood containing hypothalamic releasing and inhibiting hormones as well as posterior lobe neural hormones (antidiuretic hormone and oxytocin) to the ventricular surface for subsequent transport to cerebrospinal fluid and distribution to the brain.

The hypothalamo-hypophysial vascular relationship in Indian fresh-water goby, Glossogobius giuris (Ham.).920u.

The hypothalamo-hypophysial vascular relationship and intra-hypophysial vasculatisation have been described in order to understand the regulatory mechanism of hypothalamic control over the functions of the pituitary gland. In Glossogobius giuris, the disposition of the blood vessels in the head region is on typical teleostean pattern with certain modifications. The nucleus preopticus is supplied through the nucleus preopticus artery, a small blood vessel arising from the anterior branch of the posterior cerebral artery, whereas the pituitary gland receives blood through a pair of hypophysial arteries. The blood from the pituitary is drained off by the pituitary veins whch pour their blood into the supra-orbital sinus. The anterior cerebral vein after taking the blood from anterior part of the brain including the hypothalamus and the nucleus preopticus joins with the supra-orbital sinus. The hypothalamo-hypophysial portal system is absent in this fish. The saccus vasculosus receives blood from the posterior cerebral artery through a small blood vessel and is collected by a prominent saccus vasculosus vein which pours blood into the supra-orbital sinus before it joins the infra-orbital sinus to form the heat vein. There seems to be no physological connection between the saccus vasculosus and pituitary gland. The highly vascularised neurohypophysis interdigitate with the pars intermedia and extends upto the proximal pars distalis. The blood vessels are restricted to the neurohypophysial extensions only. However, in the rostral pars distalis the blood vessels are present but the neurohypophysis does not extend to this part. The blood capillaries enter the rostral pars distalis from the capillary network on the surface of pituitary gland along with the connected tissue covering of the pituitary. The neurohypophysis shows a greater vascularisation in comparison to that of the other glandular part of the pituitary gland. In the present study of Glossogobius giuris, though an extensive ramification of neurohypophysis occurs with the pars intermedia and the proximal pars distalis, the neurosecretory axons do not innervate the endocrine cells of the pituitary gland and the blood vessels are found restricted to the neurohypophysial extensions except that of the rostral pars distalis. The neuro-vascular way of hypothalamic control over the functions of the pituitary gland seems to be justified as the neurosecretory fibres have been found associated with the blood vessels.