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Specific in vivo binding of 3H-spiperone to individual lobes of the pituitary gland of the rat. Evidence for the labelling of dopamine receptors.

The in vivo binding of 3H-spiperone to individual lobes of the pituitary gland was studied after intravenous injections in unanesthetized male rats. The binding was found to be saturable and reversible. The percentage of total binding of 3H-spiperone that was specific binding was highest in the intermediate (approximately equal to 75%) and lowest in the posterior (approximately equal to 35%) lobes. The regional distribution of 3H-spiperone binding 1 hour after injections was the following: intermediate greater than anterior greater than posterior. Pharmacological analysis of the in vivo 3H-spiperone binding showed that dopamine agonists (e.g. bromocriptine, N-n-propylnorapomorphine) and antagonists could prevent the in vivo binding of 3H-spiperone in all three parts of the gland. The substituted benzamide drugs remoxipride and raclopride blocked the in vivo 3H-spiperone binding in the anterior and intermediate lobes but did not reduce the 3H-spiperone binding in the posterior part, except when given in very high doses. Taken together, the present study has shown that 3H-spiperone can be used in studies of the dopamine receptors in the anterior, intermediate and posterior lobes of the pituitary gland, but the proportion of non-specific binding is higher than in the striatum. The use of in vivo 3H-spiperone binding may thus be a useful method to study the regulation and pharmacology of these receptors in situ.

Animals↗

The influence of partial resection of the small intestine on the pituitary gland.

Starting from the observations of other investigators according to whom massive resection of a portion of the small intestine brings about compensatory changes in the remaining intestine, the existence of a feed-back mechanism between the small intestine and the pituitary gland is postulated. The weight and histologic aspect of the pituitary gland were studied after resection of 50 cm jejunum in the white rat. The results showed increase in the weight of the pituitary and histologic signs of hyperactivity in the anterior lobe.

Animals↗

High resolution computed tomography of the post partum pituitary gland.

Eight volunteer post partum female patients were examined with high resolution computed tomography during the week immediately after delivery. All patients received high dose (40-70 gm) intravenous iodine contrast administration. The scans were examined for pituitary gland height, shape and homogeneity. All of the patients had enlarged glands by the traditional standards (i.e. gland height of 8 mm or greater). The diaphragma sellae in every case bulged upward with a convex domed appearance. The glands were generally inhomogeneous. One gland had a 4 mm focal well defined area of decreased attenuation. Two patients who were studied again months later had glands which had returned to "normal" size. The enlarged, upwardly convex pituitary gland appears to be typical and normal for the recently post partum period.

Female↗

Intercellular communication within the rat anterior pituitary gland: IV. Changes in cell-to-cell communications during pregnancy.

Cell-to-cell communication by gap junctions was investigated in the female rat anterior pituitary gland from 9 through 21 days of pregnancy and subsequently on days 2 and 20 of the lactational period. Compared with intact estrus females, the major morphological characteristics of the pituitary gland during pregnancy were remarkably developed prolactin cells and gonadotrophs. A close relationship of both cell types was clearly evident. Gap junctions were present at each of the time intervals studied; however, they were noted only between adjacent folliculo-stellate cells. No remarkable changes were noted in the number of gap junctions during the middle stage of pregnancy (day 9 through day 15), with the relative number resembling that found in intact, 90-day-old controls during estrus (0.47 +/- .01 junctions/follicle-control vs. 0.50 +/- 0.08--day 15 of pregnancy). In the later stages of pregnancy (day 17 through day 21), a demonstrable increase was observed (0.64 +/- 0.10--day 17, 0.79 +/- 0.11--day 19 and 0.72 +/- 0.12--day 21), whereas during the lactation, this pattern returned to that seen at midpregnancy. Since both prolactin and the gonadal steroid hormones dramatically fluctuate during pregnancy and lactation, it is postulated that they may have an active role in gap junction formation during these two phases of reproductive life.

Animals↗

[Advanced transfacial approach to extensive sellar adenoma of the pituitary gland].

The excision of tumors of the pituitary gland is usually achieved via a transsphenoidal transnasal approach. In the past, alternative approaches were described for macroadenomas. Especially in tumors surrounding the internal carotid artery (ICA) and the optic nerve, the selection of the appropriate approach is of importance. We demonstrate the case of a second extensive relapse of a macroadenoma after primary transsphenoidal resection and radiation therapy. As the tumor enclosed both the ICA and left optic nerve, a median external approach via the upper midface was chosen. After the median skin incision and translocation of the upper parts of the nasal structure, the papyraceous lamina was removed bilaterally. The orbital tissue was laterally exposed with retractors, achieving a wide access to both carotids and optic nerves. The functional and aesthetic results were satisfactory. Compared with other approaches, this one provides a good exposure of both the ICA and optic nerve.

Adenoma↗

Chronic estrogen treatment promotes a functional uncoupling of the D2 dopamine receptor in rat anterior pituitary gland.

The effect of chronic estrogen treatment on the anterior pituitary D2 dopamine receptor was studied by treating rats with diethylstilbestrol (DES) over a 6-week period. DES treatment resulted in an increase in anterior pituitary weight and PRL content and serum PRL levels compared to those in sham-treated controls. The status of the anterior pituitary D2 dopamine receptor was evaluated using both radioligand binding and adenylate cyclase assays. [125I]N-(p-aminophenethyl)spiroperidol [( 125I]NAPS), a derivative of the D2-selective antagonist spiperone, was used to quantitate D2 receptors. Saturation analysis of [125I]NAPS binding indicated that DES treatment had no effect on the affinity or maximum binding capacity of the radioligand for the D2 receptor. Competition analysis with unlabeled D2 antagonists for [125I]NAPS binding also indicated that DES treatment did not affect antagonist interactions with the receptor. In contrast, the interactions of agonists with the D2 receptors from DES-treated rats were modified, as assessed through [125I]NAPS competition analysis. Using control tissue, agonist competition curves revealed both high and low affinity agonist binding states of the receptor. In the presence of guanine nucleotides, the high affinity agonist binding state is abolished, reflecting coupling of the receptor with a guanine nucleotide regulatory (G) protein. In DES-treated tissue, agonist competition curves indicated the presence of only low affinity agonist binding, with minimal effects of guanine nucleotides, suggesting uncoupling of receptor-G-protein interactions. The functionality of the D2 receptor was further assessed by examining dopaminergic inhibition of vasoactive intestinal peptide-stimulated adenylate cyclase activity. Although DES treatment resulted in a reduction of vasoactive intestinal peptide-stimulated enzyme activity itself, the ability of dopaminergic agonists to inhibit this activity was reduced by about 50%. These results suggest that estrogen is capable of attenuating the functional coupling of the D2 receptor with its biochemical effector system in the anterior pituitary gland.

Adenylyl Cyclases↗

Subhypothalamic high-intensity signals identified by magnetic resonance imaging in children with idiopathic anterior hypopituitarism. Evidence suggestive of an 'ectopic' posterior pituitary gland.

Magnetic resonance imaging in two children with idiopathic hypopituitarism demonstrated a signal of high intensity near the optic tract that was consistent with the signal produced by posterior pituitary tissue. Patient 1 was a 15-year-old girl with panhypopituitarism but intact posterior pituitary function. Computed tomography disclosed widening of the superior aspect of the pituitary stalk and a partially empty sella. Magnetic resonance imaging disclosed a 3-mm high-intensity signal abutting the optic tract in the midline just above the sella. The pituitary stalk was not clearly defined, the pituitary gland was small, and the sella was filled with cerebrospinal fluid. Patient 2 was a 12-year-old boy with isolated deficiency of growth hormone secretion. Findings from magnetic resonance imaging and computed tomography were similar to those in patient 1. These data suggest that the high-intensity magnetic resonance imaging findings represent a displaced or "ectopic" posterior pituitary gland, and that the hypopituitary state is due to an insult to the pituitary stalk.

Adolescent↗

Responsiveness of the pituitary gland to androgens and of the tests to gonadotrophins following damage to spermatogenesis in rats.

To test the interaction of androgen and inhibit feedback on the pituitary gland, inhibin-type feedback from the testes was reduced when they were made aspermatogenetic by bilateral ligation of the efferent ducts or local heating (43 degrees C for 30 min). There were only minor effects on the subsequent response of the pituitary gland to the removal of androgen feedback by the administration of antiserum against testosterone or by castration. However, in the antiserum-injected animals the steroidogenic response of the testis to the increased serum concentrations of LH was less in aspermatogenic than in control rats. Furthermore, unilateral aspermatogenesis was associated with reduced testosterone output by the treated testis and with compensatory increased output by the contralateral control testis, despite the absence of significant changes in serum LH and normal peripheral levels of testosterone. This suggests that the tubules can regulate the responsiveness of the Leydig cells to LH.

Animals↗

Ultrastructural evidence for endogenous somatostatin-like immunoreactivity in the pituitary gland.

The tetradecapeptide, somatostatin (SRIF), is a potent inhibitor on pituitary hormone release, by a direct effect. The immunocytological method was used with the aim of localizing SRIF at the cellular and subcellular levels. Rat pituitaries were fixed and frozen. Ultrathin sections obtained by cryoultramicrotomy, were incubated with anti-SRIF serum. The antigen-antibody reaction was detected by 4-chloro-1-naphthol. SRIF immunoreactivity was observed in somatotrophs, thyreotrophs and prolactin cells, but not in corticotrophs or gonadotrophs. Im immunoreactive cells, SRIF was found in the cytoplasmic matrix, in the secretory granules and in the nucleus distributed primarily in the euchromatin, in the vicinity of the heterochromatin regions. SRIF immunoreactivity was also observed at the plasma membrane. No immunoreactivity was observed when nonimmune serum or anti-SRIF serum incubated with SRIF was used. No modification was observed when anti-SRIF serum incubated with gonadoliberin, thyroliberin or vasopressin was used. These data (1) provide immunocytological evidence for the presence of somatostatin in pituitary gland, and (2) indicate the presence of SRIF peptide in the somatotrophs, thyreotrophs and prolactin cells.

Animals↗

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.

Animals↗

Influence of sex and age on T3 receptors and T3 concentration in the pituitary gland of the rat: consequences on TSH secretion.

A reduced secretion of thyroid hormones with age has been documented in humans and animals with no substantial increase in TSH secretion, which may be indicative of an age-related impairment of the pituitary sensitivity to the negative control exerted by thyroid hormones. We have evaluated in rats the influence of sex and age on pituitary T3 nuclear receptors--known to be determinant in the regulation of TSH secretion--as well as on T3 concentration in the pituitary gland. As regards sex, the density of T3 receptors and the concentration of T3 in pituitary gland and plasma were greater in females than in males whereas pituitary and plasma TSH concentrations were less. As for age, the density of T3 receptors was greater in old male rats than in young ones with no changes in pituitary T3 and plasma TSH concentrations. In old female rats in contrast, there was no significant increase in T3 receptors but pituitary T3 was less and plasma TSH greater than in young female rats. In both sexes plasma thyroid hormones and pituitary TSH were reduced with age whereas TSH response to TRH was not altered. These results illustrate sex and age differences in pituitary T3 receptors and pituitary T3 concentration as well as in TSH secretion. In young animals of both sexes an inverse correlation is observed between the density of pituitary T3 receptors and plasma TSH. In contrast, in old animals the absence of this correlation is suggestive of an age-related impairment of T3 action on the thyrotrophs or of changes pertaining to other factors modulating TSH secretion.

Aging↗

Localization and characterization of atrial natriuretic peptide binding sites in discrete areas of rat brain and pituitary gland by quantitative autoradiography.

Atrial natriuretic peptide [rat (r) ANP6-33 or ANP99-126] binding sites were localized in discrete areas of rat brain and pituitary gland using quantitative autoradiographic techniques. High numbers of rANP6-33 binding sites were concentrated in the circumventricular organs (the organon vasculosum laminae terminalis, organon subfornicalis, and area postrema) and selected hypothalamic nuclei (the nucleus supraopticus, nucleus preopticus medianus and nucleus paraventricularis). High binding was also present in the choroid plexus and the bulbi olfactorii (laminae medullaris interna). A relatively low number of rANP6-33 binding sites was observed in other olfactory, limbic and brainstem areas (the nucleus tractus solitarii, nucleus motoris dorsalis vagii and nucleus hypoglossi), the eminentia mediana and the pituitary gland (anterior and posterior lobes). High-affinity rANP6-33 binding sites were demonstrated in the organon subfornicalis and the area postrema after incubation of consecutive sections from individual rat brains with 125I-rANP6-33 in concentrations from 20 to 400 pM. rANP6-33 binding sites were concentrated in areas associated with angiotensin II and/or vasopressin, suggesting an interaction among these peptides in the central nervous system.

Animals↗

The action of 5 alpha-dihydrotestosterone and antiandrogens on the activities of 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase in the pituitary gland of gonadectomized rats.

In gonadectomized rats of either sex s.c. administration of 5 alpha-dihydrotestosterone (DHT) reversed, in a dose dependent manner, effects brought about by gonadectomy: it decreased pituitary wet weight and serum levels of LH and FSH and suppressed microsomal enzyme activities involved in testosterone and progesterone metabolism in the pituitary gland, NADPH-linked 5 alpha-reductase and NADH-linked 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSDH). Concomitantly administered nonsteroidal antiandrogen, flutamide (5 mg/day), antagonized some of the suppressive effects induced by a 14-day treatment of gonadectomized rats with high dose (1 mg/day) of DHT. It completely blocked DHT action on pituitary 5 alpha-reductase activity in the female rat and, in the male, inhibition was found to be 30-35%. In male, but not female rats, it completely blocked DHT suppression of serum FSH level whereas it slightly, but significantly inhibited DHT suppression of serum LH in rats of either sex. However, flutamide did not prevent DHT suppression of pituitary wet weight or NADH-linked 3 alpha-HSDH activity. Concomitantly administered progestational antiandrogen, cyproterone acetate (5 mg/day), inhibited DHT-induced weight increase of seminal vesicles by 50-55% and completely blocked the weight decrease of pituitary gland but did not antagonize DHT suppression of serum gonadotropins or pituitary enzyme activities. The results obtained with flutamide suggest that DHT-induced suppression of pituitary NADPH-linked 5 alpha-reductase, but not NADH-linked 3 alpha-HSDH activity, might involve an androgen receptor mechanism.

3-Hydroxysteroid Dehydrogenases↗

Distribution of adrenomedullin and proadrenomedullin N-terminal 20 peptide immunoreactivity in the pituitary gland of the frog Rana perezi.

Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two multifunctional peptides processed from a common precursor which have been described in numerous mammalian organs, including the pituitary gland. Previous studies have found AM immunoreactivity in neurohypophysis nerve fibers of amphibian pituitary. In the present study, immunocytochemical and Western blot analysis in the pituitary gland of the amphibian Rana perezi demonstrated in the adenohypophysis both AM and PAMP. AM-like immunoreactivity was found in a moderate number of endocrine cells of the pars distalis. In the neurohypophysis, AM was observed not only in nerve fibers of pars nervosa and axonal projections innervating the pars intermedia, but also in the outer zone of the median eminence. PAMP staining was observed in numerous endocrine cells scattered all over the pars distalis and in some cells of the pars tuberalis, but not in the neurohypophysis. In order to compare the quantity of AM and PAMP immunoreactivity between pars distalis of female and male specimens, an image analysis study was done. Significant differences for AM immunoreactivity (p<0.001) between sexes was found, the males showing higher immunostained area percentage. Differences of PAMP immunoreactivity were not significant (p=0.599). Western blot analysis detected bands presumably corresponding to precursor and/or intermediate species in the propeptide processing.

Adrenomedullin↗

Immunocharacteristics of oestrogen and androgen target cells in the anterior pituitary gland of the chick embryo as demonstrated by a combined method of autoradiography and immunohistochemistry.

The distribution of oestrogen and androgen target cells in the anterior pituitary gland of the chick embryo on days 10, 12 and 15 of incubation was studied 1 h after the injection of tritium-labelled steroid hormone using the thaw-mount autoradiographic technique. Oestradiol target cells were localized in the caudal zone that corresponds to the so-called 'caudal lobe', while androgen target cells were found throughout the rostral and caudal lobes of the anterior pituitary gland. With a combined autoradiography and immunohistochemistry technique, most of the oestrogen target cells showed immunoreactivity to turkey LH antiserum but not to adrenocorticotrophin (1-24) and beta-thyrotrophin antisera. In contrast, androgen target cells did not show positive immunoreactivity to the three antisera used. The results suggested a direct and early involvement of oestrogens but not of androgens in the feedback regulation of pituitary gonadotrophin secretion in the chick embryo.

Androgens↗