Hypophyseal angioarchitecture of common tree shrew (Tupaia glis) revealed by scanning electron microscopy study of vascular corrosion casts.

The vascular corrosion cast technique in conjunction with scanning electron microscopy (SEM) was used for the study of pituitary microvascularization in the common tree shrew (Tupaia glis). The pituitary vascular casts were obtained by infusion of low viscosity methyl methacrylate plastic (Batson's no.17) mixture. It was found that the blood supplies to the pituitary complex were from branches of the circle of Willis and could be divided into two groups. The first group consisted of two to four superior hypophyseal arteries (SHAs) branching off from the internal carotid artery supplying each half of the median eminence (ME), infundibular stalk (IS), and pars distalis (PD). The SHAs supplying the ME branched into internal and external capillary plexi. The internal plexus had a larger capillary size (approximately 15 microns in diameter), was deeper in position, and had denser and more complex capillary loops than those in the external plexus. The capillaries of the external plexus were approximately 10 microns in diameter. The two plexi drained into 15-20 hypophyseal portal veins (HPVs) which were located mainly along the ventral and ventrolateral surfaces of the IS before breaking up into large capillaries (approximately 18 microns in diameter) with an anteroposterior arrangement within the PD. The second group consisted of one inferior hypophyseal artery (IHA) on each side branching off from the internal carotid artery. These arteries gave off branches to pierce the dorsolateral and ventrolateral aspects of infundibular process (IP) before branching off to form a capillary network. They also gave rise to radiating capillaries to supply the pars intermedia (PI) surrounding the cortical area of the IP. The hypophyseal cleft separating the PI from the PD was clearly seen with very few blood vessels. The capillaries in both PD and IP joined to form confluent hypophyseal veins draining the blood into the cavernous sinus.     

Vascularization of the pituitary of the Australian lungfish and Neoceratodus forsteri

The vascularization of the brain and the pituitary region of the Australian lungfish, Neoceratodus forsteri is described from serial section reconstruction. The distal lobe has no direct arterial blood supply and receives blood solely from a pituitary portal system basically similar to that of other sarcopterygians. The primary capillary plexus of the median eminence receives its arterial blood from the infundibular arteries, which on their way distribute some small branches to the prechiasmatic region. The primary plexus also receives capillaries from the adjacent pial hypothalamic plexus. The primary capillary plexus of the median eminence comprises a rostral 'uncovered' and caudal 'covered' part which are not sharply delineated. Distinct portal vessels connect the 'uncovered' rostral part of the primary plexus with the secondary capillary plexus supplying the rostral subdivision of the pars distalis. The 'covered' caudal part of the primary plexus merges into the proximal subdivision of the pars distalis, apparently without formation of distinct portal vessels. The primary plexus has some connections with the plexus intermedius via a hypophysial stem capillary plexus. The plexus intermedius has a substantial arterial supply and gives off capillaries to the parenchyma of the pars intermedia. The adenohypophysis is drained into an unpaired hypophysial vein. The significance of the vascular pathways is discussed from comparative, functional, and evolutionary viewpoints.     

The Structure of the Hypothalamohypophysial Portal Vascular System in Acipenser ruthenus L. (Chondrostei)

The vascularization of the pituitary region in Acipenser ruthenus L. (Chondrostei) is described. The adenohypophysis has no direct arterial supply but is fed exclusively by a pituitary portal system supplied through a pair of infundibular arteries. Distinct portal vessels connect the lateral part of the primary plexus of the neurohaemal area (the median eminence) with the secondary plexus of the pituitary gland. The primary plexus enters the pars distalis paramedially, apparently without the formation of distinct portal vessels. The neuro-intermediate lobe receives its blood supply exclusively from the primary plexus. The plexus intermedius gives off capillaries to the parenchyma of the intermediate lobe (an intermediate lobe sinus system). The saccus vasculosus receives (1) a “direct” supply, i.e. branches originating directly from the cerebral arteries and (2) an “indirect” supply, i.e. capillaries from the primary plexus. The pars distalis is drained into an unpaired ventral hypophysial vein, while a dorsal hypophysial vein, also unpaired, drains the plexus intermedius. These two veins join to form the unpaired hypophysial vein. The findings are discussed from comparative and functional viewpoints.     

Vascular Connections in the Pituitary of Anolis carolinensis with Special Reference to the Pars intermedia

The pituitary vascular system of Anolis carolinensis is similar to that of other lizards. Distinct portal vessels connect the primary plexus of the median eminence with the secondary plexus of the pars distalis. The primary plexus has some connections with the neural lobe. The neural lobe plexus is fed by separate arteries, and drains into the pars intermedia. The latter lobe receives its blood supply by this route. The pituitary is drained into the vena retrohypophysea. The findings are discussed in relation to existing theories regarding the neurovascular control of the pars intermedia.     

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.     

Immunocytochemical localization of vimentin in the posterior lobe of the cat, rabbit and rat pituitary glands

The presence and distribution of vimentin, a subunit of intermediate filaments, in the neural lobe and in the pars intermedia of the cat, rabbit and rat pituitary glands were investigated immunocytochemically. In the pars intermedia, our study revealed the presence of vimentin in glial-like cells located between glandular secretory cells of the three species and in the cells of the marginal layer of the cat and rat hypophyseal cleft. In the neural lobe of the cat and rabbit pituitary glands, there was a large amount of cell processes and immunoreactive pituicytes. In contrast, in the rat neural lobe, few pituicytes exhibited immunoreactivity, and these were located principally in the posterior region near the pituitary stalk. The significance of immunoreactive vimentin in these cells is discussed.     

Vascularization of the hypophysial region of the normal and adenohypophysectomized toad

Summary The study of standarized sections of the hypophysial regions, and in vivo observations showed the presence of communicating vessels between the capillary network of the median eminence and the large capillaries of the neurointermediate junction. Moreover, direct branches from the hypophysial artery are described which give off branches, at the level of the neural stalk, to the median eminence and to the large capillaries of the neurointermediate junction.A second portal system similar to the one described by Cruz has been observed. Its primary plexus originates in several encephalic regions, and its secondary plexus is distributed through the neural lobe and thence to the pars intermedia. The course of flow in this system is a descending one. The arterial contribution to this system appears to arise from branches from the basilar and retroinfundibular arteries. — There are small venous-type vessels between the large capillaries of the neurointermediate junction and the posterodorsal region of the pars distalis. — After adenohypophysectomy, the blood which normally goes towards the pars distalis, flows towards the pars intermedia, following the path of the communicating vessels between the median eminence and the pars intermedia.This paper was presented at the VII Reunion de la Asociación Latinoamericana de Ciencias Fisiológicas (A.L.A.C.F.), Mar del Plata, Argentina, 1966. It was carried out under the auspices of the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina and the Rockefeller Foundation (School grant RF-58028).Fellows of the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina. — The authors wish to thank Prof. B. A. Houssay and Drs. J. H. Tramezzani and J. la Pointe for their criticism, to Prof. M. H. Burgos and Dr. F. Sacerdote for their help.     

Anterior and posterior groups of portal vessels in the avian pituitary: incidence in forty nine species.

The hypophyseal portal vessels were studied in forty nine species of birds. The primary capillary plexus in the median eminence is single or divided into an anterior and a posterior plexus. Irrespective of whether the primary capillary plexus is single or divided, distinct, non-interconnected anterior and posterior groups of portal vessels are present in all the species investigated. The anterior group of portal vessels originates in the anterior region of the median eminence and breaks up into capillaries in the cephalic lobe of the pars distalis; the posterior group of portal vessels originates in the posterior region of the median eminence and breaks up into capillaries in the caudal lobe of the pars distalis. This type of regional distribution of portal vessels appears to be of general occurrence in the avian pituitary. The median eminence in the species investigated shows an AF-positive anterior region and an AF-negative posterior region. The pars distalis is differentiated into histologically distinct cephalic and caudal lobes. The arrangement of the portal vessels into anterior and posterior groups provides morphological basis for the view that the functions of the cephalic lobe may be controlled by the anterior median eminence, whereas those of the caudal lobe may be controlled by the posterior median eminence. However, experimental data available to date do not suggest a physiological significance to the widespread incidence of the regional distribution of portal vessels in the avian pituitary.     

Ultrastructural study of the uptake of peroxidase by the rat median eminence

An active role of the ependymal cells (tanycytes) of the median eminence in the transport of hypothalamic hormones has been recently suggested. In order to investigate the fate of material present in the cerebrospinal fluid, a protein tracer, horse-radish peroxidase (HRP) was injected into the left lateral ventricle of rats. Two minutes after the injection, HRP had largely diffused between tanycytes and hypendymal cells. As soon as 5 min after the injection, HRP had completely penetrated all the layers of the median eminence. A few labelled vesicles and lysosomes were occasionally seen in ependymal and glial cells. At longer time intervals (20 min, 1 and 4 hrs), a reaction was observed in the lumen of fenestrated capillaries of the pituitary portal plexus. In many nerve endings of the external zone, vesicles and lysosomes were seen to contain HRP. An interesting observation was the localization of HRP between nerve endings and cells in both the pars nervosa and the pars intermedia of the pituitary gland. No reaction was recorded in the anterior pituitary and the kidney. Seventeen hours after the injection, the extracellular space was free of reaction but a few positive intracellular structure were still found. These results clearly indicate that some material from the third ventricle can rapidly diffuse between cells and axons of the median eminence to reach the fenestrated capillaries of the pituitary portal plexus and the posterior pituitary without involving an active transport by tanycytes.     

Structure of the neurohypophysis and the hypothalamo-hypophysial vascularization in the teleost Channa punctatus Bloch.

In C. punctatus the median eminence includes the subterminal region of the hypothalamus and the anterior neurohypophysis. It is formed of ependymal, fibrous and reticular layers as in the tetrapods. Primary capillary plexus extends from the subterminal region to the extremity of the anterior neurohypophysis. Only few portal vessels from the hypothalamus enter in the pars distalis. All the components of pituitary including the pars intermedia are irrigated by the secondary plexus formed from the portal vessels emerging out of the anterior neurohypophysis. The neurosecretory axons and the ependymal cells are in close morphological contact with the primary plexus. Several axons have perivascular endings at the median eminence. Some axons were found to be only silver or aldehyde fuchsin positive whereas some others take up both. The silver positive axons were abundant in the pars distalis and the AF positive ones were more concentrated in the pars intermedia with greater accumulation of neurosecretory material.     

Immunocytochemical study of the GABAergic innervation of the mouse pituitary by use of antibodies against gamma-aminobutyric acid (GABA)

Summary The GABAergic innervation of the mouse pituitary, including the median eminence, was studied at light microscopic and ultrastructural levels by use of a pre-embedding immunocytochemical technique with antibodies directed against GABA. In the median eminence, a high density of GABA-immunoreactive fibers was found in the external layer where the GABAergic varicosities were frequently observed surrounding the blood vessels of the primary capillary plexus. In the internal and subependymal layers, only few fibers were immunoreactive. The intense labeling of the external layer was observed in the entire rostro-caudal extent of the median eminence. In the pituitary proper, a dense network of GABA-immunoreactive fibers was revealed throughout the neural and intermediate lobes, entering via the hypophyseal stalk. The anterior and tuberal lobes were devoid of any immunoreactivity. The GABA-immunoreactive terminals were characterized in the median eminence, and in the intermediate and posterior lobes at the electron-microscopic level. They contained small clear vesicles, occasionally associated with dense-core vesicles or neurosecretory granules. In the intermediate lobe they were seen to be in contact with the glandular cells. In the posterior lobe and in the median eminence, GABA-immunoreactive terminals were frequently located in the vicinity of blood vessels. These results further support the concept of a role of GABA in the regulation of hypophyseal functions, via the portal blood for the anterior lobe, directly on the cells in the intermediate lobe, and via axo-axonic mechanisms in the median eminence and posterior lobe.     

An immunohistochemical study of adenohypophyseal cells in the viviparous reptile Chalcides chalcides

The morphology of the hypophysis and the immunocharacteristics of the adenohypophyseal cells in the viviparous reptile Chalcides chalcides were studied by light microscopy, using conventional staining methods and an indirect antibody technique (ABC method), respectively. The general morphology of the C. chalcides hypophysis was comparable to that of other reptiles, showing three main regions: the pars distalis, the pars intermedia and the pars nervosa. The gland appeared as an elongated body in a cephalic-caudal direction and was almost completely enclosed in the sella turcica. For this reason, the hypophysis was studied in toto with the brain in decalcified specimens. The pars distalis accounted for most of the whole organ. The pars intermedia surrounded the pars nervosa as a goblet. The pars tuberalis was lacking.The immunohistochemical identification of the adenohypophyseal cells was performed using rabbit antisera against mammalian/synthetic hypophyseal hormones. Prolactin cells were clustered in small cellular cordons in the rostral pars distalis and in the medial pars distalis in both male and female specimens. Somatotropic cells were found in the caudal pars distalis. Corticotropic cells were observed in the medio-rostral pars distalis, as well as in the pars intermedia, where melanotropic cells were also present. Melanotropic cells were confined to the pars intermedia. Gonadotropic cells were mostly distributed in the ventral and lateral portions of the pars distalis, where they were found isolated or in small clusters. Thyrotropic cells were detected in the pars distalis with a distribution similar to that of the gonadotropic cells; however, atypically, they were also found in the pars intermedia. Therefore, the cytological characteristics of the adenohypophyseal cells appeared mostly conserved.     

Cellular localization of monoamines in the median eminence and the infundibular stem of some mammals

Summary A histochemical analysis of the monoamines which are strongly accumulated in the median eminence and the proximal part of infundibular stem of all species examined (mouse, rat, guinea pig, hamster, rabbit, and cat) was performed with the help of a highly specific and sensitive fluorescence method. Strong evidence was obtained for the view that the monoamines are localized in very high concentrations to the terminal parts of non-sympathetic nerve fibres, which — mainly at least — converge to the primary plexus of the hypophyseal portal system. The capillaries are densely and closely surrounded by the nerve fibres.Pharmacological experiments, involving the administration of reserpine, nialamide, m-tyrosine and -methyl-m-tyrosine, furnished good evidence for the view that primary catecholamines, probably mainly DA but also NA, are the predominant monoamines present. The experiments also revealed the existence of catecholamine-containing nerve cells in the arcuate nuclei and the ventral portion of the anterior periventricular nuclei. These nerve cells, situated in the regions where the tubero-infundibular tract arises, may be the cell bodies of adrenergic neurons to which the amine-containing nerve fibres at least partly belong.The findings indicate that primary catecholamines are released to the primary plexus of the hypophyseal portal system and thus transported to the anterior lobe. These amines may consequently act as neuro-humoral transmittors for the regulation of the activity of the anterior pituitary. — No direct adrenergic innervation of the cells in the pars tuberalis and anterior lobe was found. The portal vesstes in the pars tuberalis receive a very sparse adrenergic innervation and the vessels in the anterior lobe receive no or very few adrenergic nerves. Pars intermedia, on the other hand, may have a non-sympathetic adrenergic innervation.The Following Abbreviations are Used DA Dopamine - NA Noradrenaline - A Adrenaline - 5-HT 5-hydroxytryptamine For generous supplies of drugs we are indepted to Swedish Ciba, Stockholm (reserpine), and Swedish Pfizer, Stockholm (nialamide). The investigation was supported by research grants from the United States Public Health Service (NB 02854-03), the Swedish Medical Research Council, and the Therese and Johan Andersson Memorial Foundation. The excellent technical assistance of Miss M. Gustafsson is gratefully acknowledged.     

Localization of acetylcholinesterase and choline acetyltransferase in the rat pituitary gland

Summary Experiments were conducted to determine the presence of two cholinergic biomarkers, acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) in the rat pituitary. A histochemical procedure for AChE was used to provide visualization of structures containing this enzyme. Radiochemical methods provided a sensitive assay for measuring ChAT activity. Nerve fibres staining for AChE activity were observed in the neurointermediate lobe, with the greatest concentrations appearing at the junction region with the pituitary stalk. Cells staining for AChE were found in the pars distalis and pars intermedia. ChAT activity correlated well with AChE distribution in pars nervosa and pars intermedia but not in pars distalis. The greatest levels of ChAT activity were in pars intermedia and the region where the stalk joins the pituitary. Significant values were also found for the pars nervosa. The presence of AChE and ChAT in pars intermedia and pars nervosa is evidence for a cholinergic innervation to these regions. In pars distalis, where other investigators have found muscarinic receptors, intense staining for AChE and absence of ChAT activity may indicate non-innervated, acetylcholine-sensitive sites.     

Changes in the hypothalamo-hyophyseal neurosceretory system of mammals following pituitary stalk transection and hypophysectomy]

Hypophysectomy and pituitary stalk section result in dramatic morpho-functional changes in all parts of mammalian hypothalamo-hypophyseal neurosecretory system. Reorganization of the hypophyseal stalk consists of several interconnected but differing in time processes. Simultaneously with the developing traumatic changes (degeneration of the sectioned neurosecretory fibers, secretory disorders) proliferation of pituicytes with characteristic phagocytic activity is observed. A little bit later, intensive mitotic division of endothelial cells and capillary formation piercing the stalk periphery begins. At the same time, a new way for blood outflow from the capillaries of the primary portal plexus into the synuses of the brain pias is restored. Degenerated neurosecretory fibers are gradually substituted by regenerating fibers forming a dense network in heavily vascularizated stalk parts. As differentiation of endothelial cells and regeneration of neurosecretory fibers procede, axovasal contacts are gradually forming. At that time the hypophyseal stalk begins functioning as a neurohumoral organ but morpho-functionally less perfect than the posterior hypophyseal lobule. In the median eminence of the operated animals, unlike the intact ones, neurosecrete is accumulating around the capillaries of the portal plexus. Mechanical damage of neurosecretory fibers during the operation results in degeneration of a greater number of neurosecretory cells in the supraoptical and paraventricular nuclei. Preserved cells have an increased functional activity because of neurohormonal deficiency in the organism. As a result of the structural changes mentioned, diabetes mellitus develops, subsiding gradually with time course.     

Interrelationships between pars intermedia and posterior pituitary with regard to corticotrophic and thyrotrophic partial function in rats

Functional interrelationships between the pars intermedia and posterior pituitary were proved under different experimental conditions. After stimulation of the thyrotropical axis of rats by an acute intraperitoneal application of 50 microgram TRH/rat the nuclear sizes of the thyroid follicular and the anterior pituitary thyrotropical cells increased according to a monophasic time curve with maximal amplitude at the time of 30 minutes. Interestingly, the nuclear sizes of the posterior pituitary cells were also enhanced. Under the same experimental conditions the nuclear areas of the cells of the external layer of the adrenal zona fasciculata decreased as did the nuclei of the pars intermedia cells (without regard to the cell type or localization of the cells in the intermediate lobe). Stimulation of the adrenocorticotropical axis by an acute injection of 0.2 ml isotonic saline solution/rat was followed by a time-dependent increase of nuclear sizes of the fasciculata cells and pars intermedia, whereas the nuclear volumes of the thyroid follicular cells, the anterior pituitary thyrotropical cells and the posterior pituitary cells decreased. Thus the functional state of the pars intermedia was in accordance with that of the adrenal cortex. Also the posterior pituitary cells responded to stimuli applied to the thyrotropical axis at the same degree as the thyrotropic organs themselves. Between the nuclear sizes of the pars intermedia and posterior pituitary we established the same inverse functional relationships as between the adrenal cortex and the thyroid gland.     

Vascularization of the pars intermedia of the hypophysis in the toad,Bufo bufo (L.) (Amphibia,Anura)

The vascularization of the pars intermedia of the hypophysis of the toad, Bufo bufo (L.) was studied by injection of a mixture of India-ink and gelatine into the circulatory system of the head via the arteria carotis communis. Further methyl-methacrylate corrosion casts of brains were made and the hypophysial region of the corrosion casts was examined with the scanning electron microscope. The results showed that the vascularization of the pars intermedia of the toad hypophysis consists of a single-layered vascular network, which is located on the ventral surface of the pars intermedia. The network is formed by capillaries, which primarily run caudally in a fan-like manner and which show only a few cross-connections. In the rostral region of the pars intermedia this network lies rather superficially, while in the caudal region it slightly penetrates the parenchyma. The vascular network originates from vessels of the neural stalk and from wide capillaries of the rostro-ventral region of the neurointermediate junction. The venous drainage of the pars intermedia is exerted by veins, which leave the caudal region and drain into the veins leaving the venous pole of the pars distalis. The flat, wide meshed vascular net on the ventral side of the pars intermedia, demonstrated in this study, fits into the concept that the pars intermedia of the anuran hypophysis is under the control of nerve fibers coming from the hypothalamus.     

Life span changes in the presence of alpha-melanocyte-stimulating-hormone-containing cells in the human pituitary.

Since recent circumstantial evidence has suggested possible functions of alpha-MSH in intrauterine growth and labour, the presence of this hormone in the human pituitary was determined by means of the indirect immunofluorescence procedure during development and adulthood. Cross reaction of the antibodies with other peptides was measured after which they were purified by solid phase absorption. Experiments on the rat pituitary showed that staining of alpha-MSH- and ACTH-containing cells could be obtained well until 48 h after death. In the pars distalis the ability of ACTH-containing cells to take up stain increased during the period of post-mortem storage. In the youngest human fetus studied (15 weeks) only alpha-MSH-containing cells were found in the pars intermedia and no ACTH-containing cells were observed. In the other fetal pituitaries a distinct pars intermedia containing more alpha-MSH cells than ACTH cells was found. In the pars distalis of the fetuses more ACTH- than alpha-MSH-containing cells were observed. From birth to 19 years, progressively fewer alpha-MSH containing cells could be detected in the 'zona intermedia' and pars distalis, while in adults only a few such cells were found in either area. Irrespective of age, sex, cause of death or therapy, alpha-MSH-containing cells were found in all pituitaries throughout life. The number of ACTH containing cells gradually increased in the zona intermedia and pars distalis and reached a high adult level in the latter structure. In the pituitaries of seven anencephalics, no alpha-MSH-containing cells were present. The presence of alpha-MSH in the fetal pars intermedia, the change in the ratio of the alpha-MSH/ACTH cells during the course of development, and the absence of alpha-MSH in anencephaly all support the possibility that human fetal pituitary alpha-MSH is involved in both intrauterine growth and fetal adrenal function and thus also in parturition.     

Ontogenesis of the α-MSH, β-MSH and ACTH cells in the foetal hypophysis of the rat. Correlation with the growth of the adrenals and adrenocortical activity

Pituitary sections from 15 to 21 day-old rat foetuses have been studied with the immunofluorescence technique, using antibodies anti alpha-MSH, anti beta-MSH and anti beta (1-24) ACTH. The first ACTH cells appear on day 17 of pregnancy in the pars distalis of the hypophysis and only on day 18 in the pars intermedia. beta-msh cells have been observed on day 16 in the pars anterior and on day 17 in the pars intermedia, while alpha-MSH cells appear only on day 18 and exclusively in the pars intermedia. The cytodifferentiation of the beta-MSH and ACTH cells occurs in the pars intermedia with about a 24 hours delay in comparison to that of the pars distalis. The first revealed cells are always located in the posterior half of the pituitary gland. The corticostimulating activity of the hypophysis has been tested with the fluorescence intensity of the corticotrophs, the adrenal weight, the adrenal content in corticosterone and the plasma corticosterone level. The fluorescence of the corticotrophs increases on day 18, shows a maximum on day 19 and decreases until term. The adrenal weight rises regularly between day 16 to day 20, thereafer the increase subsides. Adrenal and plasma corticosterone concentrations reach a peak on day 19 of pregnancy. These data suggest that hypophyseal corticostimulating activity is very high between days 18 and 19 and decreases between days 19 and 21.