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M Guerra and EM Rodriguez

The cell types of the pars tuberalis (PT) are the follicular cells, the pars distalis cells and the so-called PT-specific cells. The latter are distinct endocrine cells displaying melatonin receptors. Although the nature of the secretory product(s) of the PT-specific cells has not yet been clarified, the function of these cells has started to be unfolded. For practical reasons, previous authors have designated the, as yet, unidentified PT hormone(s) as tuberalin(s). PT-specific cells synthesise the common alpha subunit of the pars distalis glycoprotein hormones, and it has been suggested that tuberalin would correspond to the beta chain of a specific glycoprotein secreted by these cells. The aims of the present investigation were to identify the compounds secreted by the specific cells of bovine PT, and to establish their cellular and subcellular distribution. For this purpose, proteins secreted into the culture medium of PT explants were separated by electrophoresis and used to raise antibodies. Two of these proteins, with an apparent molecular mass of 21 and 72, generated antibodies (Ab-21 and Ab-72) that differentially immunoreacted with PT-specific cells. These two antibodies were used for immunoblotting of conditioned medium and of PT explants, and for light and electron microscopy immunocytochemistry. In immunoblots, Ab-21 reacted with compounds of 21, 22, 47 and 52 kDa, whereas Ab-72 revealed a compound of 72 kDa only. Ab-72 immunoreactive material corresponded to a protein, here designated as tuberalin I, secreted by a small population of PT-specific cells (type 2 cells), and stored in 140 nm secretory granules. Immunoreactive tuberalin I was missing from bovine pars distalis and from rat PT. The predominant population of PT-specific cells (type 3 cells) secreted and stored, within 280 nm secretory granules, an Ab-21 immunoreactive protein, here designated as tuberalin II. All cells of rat PT immunoreacted with Ab-21. In the cells of bovine and rat PT, immunoreactive tuberalin II was mostly confined to a paranuclear spot; this spot also bound wheat germ agglutinin and reacted with an antibody against the alpha chain of glycoprotein pars distalis hormones. It is suggested that tuberalin II would correspond to the beta chain of a specific glycoprotein secreted by type 3 PT-specific cells. In bovine PT, the cells displaying immunoreactive tuberalins I and II did not react with any of the antibodies against pars distalis hormones.

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Laboratorio de Investigaciones Endócrino–Oncológicas, Instituto de Histología y Embriología, Facultad de Ciencias Médicas, U.N.C. Mendoza, Argentina

(Received 6 August 1975)



Introduction 408

Electron microscopy of intraependymal and intraventricular nerve fibres 408

Ultrastructure of nerve fibres reaching the IIIrd ventricle 408

Fibres containing neurosecretory granules 408

Fibres containing dense-cored and/or clear vesicles 409

Fibres with few or no secretory inclusions 409

Ultrastructure of nerve fibres reaching ventricular cavities other than the IIIrd ventricle 409

Ultrastructure of nerve fibres closely associated with the ependyma but which do not reach the ventricular cavities 409

Ependymal specializations 410

Secretory ependyma 410

Subcommissural organ 410

Ependyma of the suprachiasmatic recess of the IIIrd ventricle 410

Ependyma of the infundibular recess 410

Other regions of the ventricular walls 411

The pineal gland 411

Transporting ependyma 411

Ependyma of the median eminence 412

Ependyma of the neural lobe 413

Ependyma of the neural stalk 413

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Dramatic changes have been observed at the light microscopic and ultrastructural levels in the neurosecretory axons of the distal stump of the transected proximal neurohypophysis (Dellmann & Owsley, 1968, 1969; Sterba & Brückner, 1969; Dellmann & Rodriguez, 1970). Besides phagocytic pituicytes (Dellmann & Owsley, 1968, 1969; Sterba & Brückner, 1969), large cells have been reported to occur in the median eminence (Dellmann & Owsley, 1968), characterized by a very light-staining cytoplasm and granules stainable with paraldehyde fuchsin. This report deals with the ultrastructure of these cells and their possible significance.

The investigations were carried out on grass frogs, Rana pipiens, killed 6 and 12 hr., 1, 1·5, 2, 6 and 9 days after transection of the proximal neurohypophysis. The areas adjacent to the lesion were fixed in situ with a threefold aldehyde mixture (Rodriguez, 1969), carefully dissected out and processed according to the procedure described elsewhere (Dellmann & Rodriguez, 1970);

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Acetic acid extracts of toad choroid plexuses had an antidiuretic effect in water-loaded ethanol-anaesthetized rats, whose pattern was similar to that produced by toad neural lobe extracts and by arginine vasopressin. The antidiuretic activity of the choroid plexus extracts was completely abolished by treatment with sodium thioglycollate. Antidiuretic activity per milligram choroid plexus was about four times higher in the plexus of the third ventricle than in the plexus of the fourth ventricle. The antidiuretic activity of both choroid plexuses increased progressively during the summer and autumn and reached its peak in October; it then fell to very low or undetectable levels during the middle of the winter and spring.

The choroid plexuses also showed seasonal variations in their ultrastructural organization, which might be related to the seasonal variations of their antidiuretic activity.

The origin of the substance(s) responsible for the antidiuretic activity in the choroid plexuses is discussed.

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Julie Rodriguez and Nathalie M Delzenne

The gut microbiota is now widely recognized as an important factor contributing to the regulation of host metabolic functions. Numerous studies describe an imbalance in the gut microbial ecosystem in response to an energy-dense diet that drives the development of metabolic disorders. In this context, the manipulation of the gut microbiota by food components acting as prebiotics appears as a promising strategy. Several studies have already investigated the beneficial potency of prebiotics, mostly inulin-type fructans, on host metabolism and key intestinal functions including gut hormone release. For the last 20 years, several non-digestible compounds present in food have been shown to modulate the gut microbiota and influence host metabolism in essential organs involved in the control of energy homeostasis. To date, numerous reviews summarize the impact of prebiotics on the liver or the brain. Here we propose to describe the mechanisms by which prebiotics, through modulation of the gut microbiota and endocrine functions, modulates the metabolic cross-talk communication between the gut, the adipose tissue and skeletal muscles.

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The effects of an injection of vinblastine (Vbl) into the median eminence on the structure, fine structure and antidiuretic hormone (ADH) content of the hypothalamo-neurohypophysial system in the rat is reported. The animals were studied on days 3, 8 and 25 after the injection of 1 or 5 mm-Vbl (3 μl). Significant changes were observed only in the 5 mm-Vbl-injected animals. Their median eminence extracts showed a progressive accumulation of ADH whereas ADH depletion occurred in the neural lobe extracts. On day 8 after injection, the animals exhibited strong polidipsia although considerable amounts of ADH still remained within the neural lobe. The ADH content of the plasma samples was consistently below the sensitivity of the method (5 μu.). The light microscopic analysis showed accumulation of Gomori-stainable products in the median eminence and a striking depletion of this material from the neural lobe. Electron microscopy revealed accumulation of neurosecretory vesicles and other inclusions proximal to the site of injection in the median eminence together with some evidence of nerve fibre degeneration. Few neurosecretory terminals were found in the neural lobe of the 8-day experimental rats. They had been engulfed by pituicytes for digestion. Recuperation of the normal ADH content of both median eminence and neural lobe was found to occur on day 25 after the Vbl injection. Simultaneously, the neural lobe refilled with Gomori-positive materials and neurosecretory terminals reappeared. The results suggest (1) reversible blockade of axoplasmic transport at the site of the Vbl injection; (2) reversible degeneration of neurosecretory terminals and (3) reversible blockade of ADH release in the surviving terminals of the neural lobe.

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E. Aguilar, M. L. Rodríguez-Padilla, and L. Pinilla


Prolactin has been involved in different types of hypertension both in man and in rats. In an attempt to substantiate this hypothesis, we have analysed the correlation between plasma concentrations of prolactin and systolic blood pressure (SBP) in female and male rats from spontaneously hypertensive (SH) and normotensive Wistar–Kyoto strains (30, 60 and 90 days old), as well as in adult female Wistar rats rendered hyperprolactinaemic by the administration of 100 μg testosterone propionate on day 1 of life, or adult males with low plasma concentrations of prolactin after administration of bromocriptine (4 mg/kg per day) over 15 days. Our results indicate a lack of correlation between plasma concentrations of prolactin and SBP since plasma concentrations of prolactin were normal in male and female SH rats and hyper- and hypoprolactinaemia did not affect SBP.

In spite of these normal plasma concentrations of prolactin, SH rats showed subtle changes in the secretion of this hormone in vitro and in vivo in response to exogenous serotonin administration and to immobilization.

Journal of Endocrinology (1990) 125, 359–364

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J Rodriguez-Arnao, J Miell, M Thomas, A M McGregor, and R J M Ross


Changes in thyroid status have a major effect on the GH/insulin-like growth factor (IGF) axis. The majority of IGF in the circulation is bound to specific IGF-binding proteins (IGFBPs) of which six have been cloned and sequenced. We have studied changes in hepatic gene expression of IGFBP-1, -2 and -3, in male Wistar rats rendered hyperthyroid (thyroxine, 200 μg/kg per day) or hypothyroid (propylthiouracil, 0·1% daily). Littermates of the same age were used as controls (n=6 in each group). Thyroxine was measured by radioimmunoassay, and hepatic IGFBP-1, -2 and -3 mRNA levels by Northern blot analysis using specific rat cDNA probes with a 28S ribosomal probe as a loading control. Mean± s.e.m. thyroxine levels were 247·0±44·5 (hyperthyroid group), <9·0 (hypothyroid group) and 76·0 ± 4·5 nmol/l (control group). IGFBP-1 and -2 mRNA levels in the hypothyroid animals compared with the controls were significantly increased, but similar levels of expression were found in thyrotoxic and control rats. IGFBP-3 mRNA levels in hypothyroid animals were decreased, and increased in thyrotoxic animals. Thus, in the adult rat, hypothyroidism is associated with increased hepatic IGFBP-1 and -2 gene expression, but decreased IGFBP-3 gene expression, while in thyrotoxicosis there are normal IGFBP-1 and -2 mRNA levels but increased IGFBP-3 gene expression. These results suggest that there is specific and different transcriptional regulation for IGFBP-1, -2 and -3 in hypoand hyperthyroid rats.

Journal of Endocrinology (1994) 140, 251–255

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M. Rodriguez-Padilla, C. Bellido, L. Pinilla, and E. Aguilar


Weights of testes, seminal vesicles, ventral prostate and pituitary, plasma testosterone and LH concentrations, pituitary LH content and concentration, the LH in-vivo response after LHRH administration (1 μg), and basal and LHRH-stimulated secretion in vitro were analysed in adult male spontaneously hypertensive (SH) and normotensive control (WKY) rats.

Spontaneously hypertensive rats showed: (1) testis and pituitary hypertrophy; (2) seminal vesicle and ventral prostate atrophy; (3) increased plasma testosterone and LH concentrations; (4) increased pituitary LH content and concentration; (5) unchanged net increase of plasma concentrations of LH 15 and 45 min after administration of 1 μg LHRH; and (6) increased basal LH secretion in vitro with a normal response to LHRH stimulation.

These results provide evidence that SH rats show increased LH secretion with a normal response to LHRH stimulation. The coexistence of high plasma concentrations of testosterone with seminal vesicle and ventral prostate atrophy suggest a reduction in the effectiveness of testosterone in these structures.

J. Endocr. (1987) 113, 255–260

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Two hypophysial partes distales were grafted under the kidney capsule of intact female rats. The plasma prolactin levels 15, 45 and 90 days after the operation were determined. At the same postoperative intervals the grafted glands of some of the operated rats were processed for conventional light and electron microscopy and for the demonstration of prolactin, FSH and LH according to the unlabelled immunoperoxidase procedure. The ultrastructural characteristics of the transplanted secretory cells and the amount and distribution of the immunoreactive material within their cytoplasm were used to evaluate approximately the secretory activity of these cells.

Although levels of prolactin in the three experimental groups were significantly higher than those in control rats, a decrease in prolactin level was detected in 71% of the samples taken 45 days after operation. At day 15 the graft was completely surrounded by lymphoid cells whereas at day 45 these cells had invaded the whole graft. In the group sampled at day 90 the graft was free of lymphoid cells. When traced immunocytochemically the three types of cells followed different patterns of evolution after transplantation. Most prolactotrophs were hypertrophied in all groups but, in addition, they underwent a process leading to hyperplasia some time between days 45 and 90 after operation. Syncytial formations which probably correspond to multinucleated prolactotrophs were present only in the group sampled at day 90. The number of LH and FSH cells had decreased in the group at day 45 and by day 90 the former remained scarce but immunoreactive FSH cells were no longer found. At the ultrastructural level clear signs of involution of gonadotrophs and degradation by macrophages were seen in the graft 45 days after operation.

The relation between the morphology and hormone content of the graft and hormone content of the plasma is discussed, together with several questions raised by the results. Pituitary transplantation can be used as an experimental model only if the time-dependent changes described here are taken into account.