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The neurohypophysis is a crucial component of the hypothalamo-pituitary axis, serving as the site of release of hypothalamic neurohormones into a plexus of hypophyseal capillaries. The growth of hypothalamic axons and capillaries to the forming neurohypophysis in embryogenesis is therefore crucial to future adult homeostasis. Using ex vivo analyses in chick and in vivo analyses in mutant and transgenic zebrafish, we show that Fgf10 and Fgf3 secreted from the forming neurohypophysis exert direct guidance effects on hypothalamic neurosecretory axons. Simultaneously, they promote hypophyseal vascularisation, exerting early direct effects on endothelial cells that are subsequently complemented by indirect effects. Together, our studies suggest a model for the integrated neurohemal wiring of the hypothalamo-neurohypophyseal axis.

Fusion imaging of 3D MR cisternography/angiography was used for the assessment of the vascular bulging finding detected by MR angiography from the viewpoint of the outer wall configuration of the corresponding internal carotid artery depicted by MR cisternography. With a fusion image, useful information was obtained to distinguish an infundibular dilation and enlarged origin of the normal posterior communicating artery from an aneurysm. This imaging technique can be a feasible addition to a noninvasive screening of cerebrovascular lesions with MR angiography alone.

Central diabetes insipidus (CDI) has been linked to vascular central nervous system damage, although the pathophysiology of the mechanism has never been perfectly understood. Indeed, the vascular system of human pituitary gland has rarely been the subject of rigorous investigation except at postmortem. Recently, studies of pituitary gland blood supply have been carried out by means of a time evaluation of pituitary gland enhancement with noninvasive dynamic magnetic resonance (MR) imaging after contrast medium injection. In the present study, we decided to investigate the status of posterior pituitary blood supply by evaluating vascular pituitary patterns in a group of 19 patients with idiopathic CDI in whom previous standard MR imaging had failed to identify causal specific lesions. The control group was composed of 55 subjects with a median age of 12 yr (range, 4.2-17 yr) who had idiopathic isolated GH deficiency and normal pituitary morphology and 15 young adults (18-25 yr) who had normal pituitary gland and no endocrine dysfunction. Nineteen patients (12 females and seven males), ranging in age at the time of diagnosis of CDI from 0.5-14.9 yr (median, 5 yr), were examined with dynamic MR imaging between 1990 and 1997 at a median age of 14.1 yr (range, 5.0-26.3 yr). CDI was diagnosed according to clinical findings of polyuria and polydipsia, water deprivation test, and desmopressin acetate therapeutic trial. All of the patients had permanent CDI and were being treated with satisfactory results with desmopressin, two to three times daily, either intranasally or orally. The previous MR imaging findings of the 19 CDI patients had shown the absence of posterior pituitary hyperintensity, normal pituitary stalk, and normal anterior pituitary size. Enhancement of the straight sinus, representing a temporal reference point and occurring in normal subjects simultaneously to that of the posterior pituitary gland, was observed in all subjects after iv gadopentetate dimeglumine administration, with no substantial differences between patients and controls. However, the enhancement of the posterior pituitary lobe occurred simultaneously with the enhancement of the straight sinus in all of the controls but in only 14 of the 19 patients with CDI. In the remaining five patients, the enhancement of the straight sinus was not associated with the expected contrast enhancement of the posterior pituitary gland, suggesting abnormal blood supply to the posterior pituitary lobe. This is in keeping with vascular impairment of the inferior hypophyseal artery system and suggests that abnormal blood supply to the posterior pituitary gland is associated with what, until now, has been considered idiopathic CDI.

Microvascular corrosion casts of the pituitary gland of one to nine-day-old chickens (Gallus domesticus, white leghorn hybrids) were analysed with the scanning electron microscope. Results show that the chicken median eminence is supplied by branches of the infundibular and the neural-lobe arteries. They form a flat two-dimensional primary capillary plexus, which lacks any capillary loops and is continuous with the plexus in the neural lobe. The capillaries occupy about 60% of the total area of the median eminence. A subependymal plexus is present, showing no contact with the plexus of the median eminence. The chicken neural lobe consists of many hollow buds. These buds are supplied by branches of the neural-lobe artery, which gives rise to a two-dimensional capillary meshwork similar to that of the median eminence. An anterior group of portal vessels, comprising 14-16 vessels with a mean diameter of 37 microns, and a posterior group of portal vessels, comprising 2-4 shorter and slightly thinner vessels, arise from the median eminence are the sole blood supply for the adenohypophysis (distal lobe). Anterior portal vessels supply the cephalic lobe and the most rostral area of the caudal lobe, and posterior portal vessels supply the caudal lobe of the distal lobe. There are no short portal vessels connecting the neural lobe with the distal lobe. The (sinusoidal) capillary bed of the distal lobe is laminated. The chicken hypophysis drains into the cavernous sinus, which empties into the cerebral carotid veins. Within the period studied (days 1-9 after hatching) no age-related changes were found.

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.

Blood vascular beds of the rat pituitary intermediate lobes were reproduced by injection of low viscosity methacrylate media, and then observed with a scanning electron microscope. Although the intermediate lobes of newborn and pubescent rat were poorly vascularized, the adult rat intermediate lobe contained numerous capillaries forming a fairly independent network whose density, however, was not so great as in the anterior and posterior lobes. The vascular network of the intermediate lobe could be divided into two parts: a superficial plexus close to the anterior lobe, and a deep one close to the posterior lobe, though the two plexuses were continuous with each other. The superficial plexus consisted of anastomosing capillaries, and the deep one of non-anastomosing capillaries with a palisade-fashioned arrangement. The superficial plexus seemed crucially important for the blood supply of the intermediate lobe since it developed or thickened as the animals aged. The superficial plexus received its proper afferent vessels from the middle and posterior hypophyseal arteries and emitted its proper efferent vessels continuous with the sinusoidal capillaries of the anterior lobe. The capillaries of the deep plexus usually communicated with the arterial capillaries of the posterior lobe and possibly represented another afferent route to the superficial plexus. This paper, thus, strongly suggests a portal circulation from the intermediate lobe to the anterior lobe though its functional significance is unknown.

Neurohypophyseal blood flow was studied using radiolabelled microspheres in 13 dogs. Hypoxic hypoxia and carbon monoxide hypoxia with similar arterial oxygen contents (CaO2, approximately 8 vol %) were produced. Under conditions of hypoxic hypoxia, 100-200% increases in blood flow in caudate nucleus, white matter, neurohypophysis, and all other brain regions occurred. Similar blood flow responses were observed with carbon monoxide hypoxia in all brain regions except the neurohypophysis. The role of carotid and aortic chemoreceptors in mediating this blood flow response was studied in 6 additional dogs. Similar degrees of hypoxic hypoxia were produced in chemoreceptor-intact and completely denervated animals (CaO2 approximately 8 vol %, PaO2 approximately 33 mm Hg). Hypoxic hypoxia produced a 250% increase in neurohypophyseal blood flow and a concurrent rise in plasma arginine vasopressin from 8 +/- 3 to 52 +/- 8 pg/ml. Chemoreceptor denervation completely inhibited the increase in neurohypophyseal blood flow associated with hypoxic hypoxia. Arginine vasopressin was not increased by hypoxic hypoxia under conditions of complete denervation. A unique role for peripheral chemoreceptors in regulating neurohypophyseal blood flow is postulated.