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PubMed2001

Hedgehog signaling is required for pituitary gland development.

Pituitary gland development serves as an excellent model system in which to study the emergence of distinct cell types from a common primordium in mammalian organogenesis. We have investigated the role of the morphogen Sonic hedgehog (SHH) in outgrowth and differentiation of the pituitary gland using loss- and gain-of-function studies in transgenic mice. Shh is expressed throughout the ventral diencephalon and the oral ectoderm, but its expression is subsequently absent from the nascent Rathke's pouch as soon as it becomes morphologically visible, creating a Shh boundary within the oral epithelium. We used oral ectoderm/Rathke's pouch-specific 5' regulatory sequences (Pitx1(HS)) from the bicoid related pituitary homeobox gene (Pitx1) to target overexpression of the Hedgehog inhibitor Hip (Huntingtin interacting protein) to block Hedgehog signaling, finding that SHH is required for proliferation of the pituitary gland. In addition, we provide evidence that Hedgehog signaling, acting at the Shh boundary within the oral ectoderm, may exert a role in differentiation of ventral cell types (gonadotropes and thyrotropes) by inducing Bmp2 expression in Rathke's pouch, which subsequently regulates expression of ventral transcription factors, particularly Gata2. Furthermore, our data suggest that Hedgehog signaling, together with FGF8/10 signaling, synergizes to regulate expression of the LIM homeobox gene Lhx3, which has been proved to be essential for initial pituitary gland formation. Thus, SHH appears to exert effects on both proliferation and cell-type determination in pituitary gland development.

Animals↗
PubMed1996

Indium-111-DTPA-octreotide uptake measured in normal and abnormal pituitary glands.

UNLABELLED: Pituitary uptake of [111In-DTPA]-octreotide is highly variable, and no formal methods for quantification have been described. Conflicting results have therefore been published as to the presence of somatostatin receptors in nonsecreting adenoma of the pituitary gland. The aim of the present study was to define the most accurate method for the analysis of [111In-DTPA]-octreotide SPECT studies of the pituitary gland. METHODS: We used a multidetector brain SPECT camera to measure pituitary uptake of [111In-DTPA]-octreotide in healthy volunteers and patients with and without pituitary adenoma. For quantification, two methods were compared, one involving a manually drawn ROI and one a fixed ROI, as to their reliability and discriminative power. The optimal time interval after injection was also studied in the volunteers. RESULTS: Optimal images were obtained 24 hr after injection. Correction for background activity is not useful in view of the very low counts at that time which result in highly fluctuating ratios. Lower variability was observed in the fixed ROI method in which activity was expressed as counts corrected for dosage and body weight. CONCLUSION: A fixed ROI method without background correction is the most reliable way to measure pituitary uptake of [111In-DTPA]-octreotide. This method allows for good separation of somatostatin-receptor-positive adenomas from normal pituitary glands.

Adenoma↗
PubMed2006

Development and sexual dimorphism of the pituitary gland.

The pituitary gland plays a central role in sexual development and brain function. Therefore, we examined the effect of age and gender on pituitary volume in a large sample of healthy children and adults. Volumetric magnetic resonance imaging (MRI) was conducted in one hundred and fifty four (77 males and 77 females) healthy participants. Males were between the ages of 7 to 35 years (16.91+/-5.89 years) and females were 7 to 35 years of age (16.75+/-5.75 years). Subjects were divided into subgroups of age (7 to 9, 10 to 13, 14 to 17, 18 to 21, 22 and older) and sex (male/female). Pituitary gland volume differed between sexes when comparing the age groups (F=3.55, df=2, 143, p=0.03). Females demonstrated larger pituitary glands than males in the age 14 to 17 year old groups (p=0.04). Young (19 years and under) and old (20 years and older) females demonstrated a correlation between pituitary volume and age. Males did not show this relationship. These findings provide additional evidence for gender differences in the normative anatomy of the pituitary and may have relevance for the study of various childhood onset neuropsychiatric disorders in which pituitary dysfunction has been implicated.

Adolescent↗
PubMed1981

The direct effect of reserpine in vitro on prolactin release from rat anterior pituitary glands.

Anterior pituitary glands from normal untreated rats synthesize and release the hormone prolactin (Prl) during incubation under in vitro conditions. Addition of dopamine (DA) greatly inhibits the release of Prl and to a lesser extent reduces Prl synthesis. When pituitary glands are incubated in the presence of reserpine, there is a similar significant dose-related inhibition of Prl release. This effect persists even in the presence of a DA antagonist (haloperidol) and after the depletion of hypothalamic amines by in vivo treatment with reserpine. Reserpine in vitro also inhibits release of newly synthesized growth hormone from the pituitary glands of male rats; however, this is not observed when female rats are studied. We conclude that the direct effect of reserpine to inhibit Prl release is apparently independent of any interaction with catecholamine systems and is mediated by other, presently undefined mechanisms.

Animals↗
PubMed1988

Immunocytochemical studies on the pituitary gland and spontaneous pituitary tumors of Sprague-Dawley rats.

The review of our studies indicates a predictive value of the pituitary gland and spontaneous pituitary tumors of Sprague-Dawley rats for detecting and evaluating the effects and interactions of estrogens and dopamine agonists on the pathogenesis, functional morphology and therapy of human pituitary tumors, such as prolactinomas, gonadotroph adenomas and null cell adenomas. The functional classification of spontaneous pituitary tumors in old female Sprague-Dawley rats reveals a diversity of hormone content and morphologic appearance. They seem to be useful models of the human disease.

Animals↗
PubMed1986

Pituitary dwarfism: CT evaluation of the pituitary gland.

The pituitary glands of 12 patients, aged 4-20 years, with pituitary dwarfism and of 15 age-matched control patients were evaluated with contrast-enhanced, high-resolution computed tomography (CT). In control patients, CT clearly demonstrated pituitary glands and stalks, 2.5-9.0 mm in height (average, 5.7 mm +/- 1.8). In the 12 patients with pituitary dwarfism, CT did not demonstrate the gland or stalk in four; CT faintly showed only the stalk in another four and showed a small gland (less than 2 mm in height) and a small to normal stalk in the remaining four. Eleven of the 12 patients had a birth history of breech presentation. Possible causes of pituitary dwarfism are discussed.

Adolescent↗
PubMed1997

Organisation of basement membrane components in the human adult and fetal pituitary gland and in pituitary adenomas.

Cell-matrix interactions undoubtedly have a role in the development and maintenance of the complex nonrandom structure of the human pituitary gland. We have extended previous studies by documenting the patterns of immunoreactivity for type IV collagen, laminin and fibronectin in the fetal gland, comparing these with the adult patterns. In both we have examined the differences between the anterior lobe and intermediate zone in an attempt to elucidate the apparent differences in functional response between corticotrophs in the two areas. We have also examined expression of these proteins in a series of pituitary adenomas. Finally, we have immunolocalised beta 4 integrin, a component of the alpha 6 beta 4 laminin receptor, in the adult gland and in adenomas. In the anterior lobe of the adult gland, type IV collagen and laminin were present in both epithelial and vascular basement membrane. Fibronectin was related to the basement membrane but showed a less continuous distribution. beta 4 Integrin was expressed on the basal aspects of pituitary cells, in association with laminin, suggesting that this did identify the alpha 6 beta 4 laminin receptor. In addition, immunoreactivity was present on the lateral margins of some pituitary cells, which might indicate a role in cell-cell adhesion. None of the proteins showed specific association with any particular cell type, suggesting that these specific interactions do not regulate differentiation. This pattern of expression had developed in the fetal gland by the second trimester, with expression relating to vessels preceding that in epithelial basement membrane. Type IV collagen, laminin and fibronectin were also expressed in epithelial and vascular basement membrane in the intermediate zone of the adult gland, and around Rathke's cleft in the fetal gland. However, the organisation differed, with larger groups of cells enclosed within a single basement membrane. Possible vascular connections demonstrated between the posterior lobe and the intermediate zone would permit access of posterior lobe hormones to this zone. Our data confirmed disruption of expression in pituitary adenomas, type IV collagen, laminin and beta 4 integrin having a mainly perivascular distribution, with more variable immunoreactivity for fibronectin.

Adenoma↗
PubMed1980

Effects of tri-iodothyronine, thyroxine and isopropyl-di-iodothyronine on thyroid-stimulating hormone in serum and pituitary gland and on pituitary concentrations of prolactin, growth hormone, luteinizing hormone and follicle-stimulating hormone in hypothyroid rats.

Replacement of the 3'-halogen of the tri-iodothyronine (T3) molecule by a propyl-group produces a thyromimetic analogue, 3'-isopropyl-3,5-di-iodo-L-thyronine (T2iPr), with high biological potency. A serum thyroid-stimulating hormone (TSH) suppression test with one single intraperitoneal injection of 3 or 30 nM-T3 or T2iPr or with 30 or 300 nM-thyroxine (T4) per kg body weight was performed on 56 adult male Lewis rats which were maintained for 3 weeks on an iodine-deficient diet containing 0.2% 6n-propyl-2-thiouracil (PTU). Blood was withdrawn from each rat by cardiac puncture 24 h before and 3, 7, 24 and 48 h after application of the iodothyronines. Raised serum levels of TSH, due to the treatment with PTU, were significantly reduced within 3 h of treatment with 30 nM-T3, 300 nM-T4, 3 or 30 nM-T2iPr and they remained low throughout the observation period. Treatment with 3 nM-T3, or 30 nM-T4 per kg body weight was less effective. Pituitary concentrations of growth hormone, TSH, prolactin and FSH were significantly reduced by the treatment with PTU. There was also a slight, but insignificant reduction of pituitary concentrations of LH. Treatment with T3, T4 or T2iPr stimulated the reaccumulation of growth hormone, TSH, prolactin, LH and FSH in the pituitary gland.

Animals↗
PubMed2001

Pituitary gland height evaluated by MR in patients with beta-thalassemia major: a marker of pituitary gland function.

In transfusion-dependent beta-thalassemia major, increased iron deposition in the pituitary gland has a cytotoxic effect leading mainly to hypogonadotropic hypogonadism. Our purpose was to assess in these patients the height of the pituitary gland and to evaluate whether it represents a marker of pituitary gland function. In 29 patients with beta-thalassemia major and 35 age- and gender-matched controls the pituitary gland height was evaluated in a midline sagittal scan using a spin echo T1 -weighted (500/20 TR/TE) sequence. In all patients, an extensive endocrine evaluation was performed, including measurements of spontaneous and stimulated levels of gonadotropins, thyroid hormones, growth hormone, insulin-like growth factor, and adrenal hormones. The pituitary gland height was lower in thalassemic patients with hypogonadotropic hypogonadism (n = 15) (mean 3.48; SD 0.46) than in the age- and gender-matched controls (mean 6.29; SD 0.77), (P < 0.001). No statistically significant difference was found between thalassemic patients without hormone dysfunction (n = 14) (mean 5.34; SD 1.52) and age- and gender-matched controls (mean 5.91; SD 1.06). We conclude that in thalassemic patients the pituitary gland height is an additional marker of pituitary gland function and might be useful in clinical management.

Adolescent↗
PubMed1977

Ultrastructural and physiological studies of the stalk-sectioned rat pituitary gland.

A pituitary stalk-section rat model was prepared that would be suitable for the study of the direct effects of steroids on the pituitary gland. In this model, the hypophyseal stalk was severed surgically and metal foil was inserted to prevent regeneration of portal vessels. The major portion of the pituitary no longer had a direct communication with the hypothalamus, and the only blood supply was from short portal vessels that supply the dorsolateral part of the gland. The effectiveness of the lesion was demonstrated by very high levels of serum prolactin and very low FSH and LH. Light microscopic examination revealed a large infarct in the central region of the gland with stainable cells in the peripheral area. Fourteen days after stalk-section, the infarct had shrunken appreciably, and after 21 days it was replaced by a scar. Ultrastructural studies revealed the presence of functional mammotropes in the peripheral regions of the pituitary gland, while other cells were smaller, less active, and contained fewer secretory granules. After LHRH administration there was an increase in serum LH, thus indicating the presence of a substantial number of viable gonadotropes. This was confirmed by the ultrastructural findings which now showed the appearance of large, well-granulated gonadotropes. When LHRH was given to estradiol 17-beta primed ovariectomized stalk-sectioned rats, there was a great augmentation of LH release, and many castration cells were now apparent. Therefore, the administration of estrogen and LHRH was needed for the gonadotropes of the isolated pituitary to function optimally in the synthesis and secretion of FSH and LH. The stalk-sectioned animal model permits evaluation of pituitary function isolated from hypothalamic control while it leaves the surviving pituitary gland in its normal anatomical position.

Animals↗
PubMedDate not supplied

Dynamic magnetic resonance imaging of the normal canine pituitary gland.

The pituitary glands of six normal dogs were evaluated using dynamic magnetic resonance imaging. T1 weighted images were obtained every 13 seconds for three minutes of three contiguous slices through the pituitary gland following a bolus intravenous injection of gadolinium-DTPA. Contrast enhancement was seen initially in the region of the pituitary stalk at 52-65 seconds followed by uniform enhancement at 104-143 seconds post injection. This pattern of enhancement was seen in all subjects and is similar to that reported in humans.

Animals↗
PubMed1990

Immunocytochemical and in situ hybridization studies of peptidylglycine alpha-amidating monooxygenase in pituitary gland.

The pituitary gland contains high levels of peptidylglycine alpha-amidating monooxygenase (PAM) activity and mRNA. Using affinity-purified rabbit polyclonal antisera generated to synthetic PAM peptides and PAM RNA probes, immunocytochemical and in situ hybridization studies were conducted to determine the tissue disposition and cell types expressing PAM in the adult male rat pituitary gland. PAM immunoreactivity was present at varying levels in nearly all of the anterior pituitary cells; one cell population stained intensely, while others stained moderately or weakly. These results correlated well with in situ hybridization studies that demonstrated high levels of PAM mRNA in a subpopulation comprising approximately 10-15% of the anterior pituitary cells. Based upon immunocytochemistry, intermediate pituitary lobe cells were divided into an intensely stained and a moderately stained group. PAM staining was also present in neural lobe fibers. Immunocytochemical staining of serial pituitary tissue sections for PAM and other pituitary hormones demonstrated that the anterior pituitary cells intensely stained for PAM represented a subpopulation of the gonadotropes. PAM was also identified at moderate levels in corticotropes and at lower levels in sommatotropes and lactotropes. These results suggest that many anterior pituitary cells are capable of producing amidated peptides along with their major peptide hormone.

Adrenocorticotropic Hormone↗
PubMed2004

Intrapituitary regulatory system of proliferation of mammotrophs in the pituitary gland.

Anterior pituitary cells produce growth factors plus cytokines and their receptors. Although some of these pituitary growth factors and cytokines are known to be involved in the control of cell differentiation, proliferation and hormone production in the pituitary gland, their physiological roles remain unknown. Lots of evidence indicates that they are involved in the regulation of prolactin-secreting mammotroph cell proliferation. The regulation of mammotroph functions is a suitable system for understanding the intrapituitary regulatory system operated by growth factors and cytokines, since mammotrophs are the most actively proliferating cells in female pituitary glands. This review discusses the possible intrapituitary regulation of mammotroph differentiation and proliferation in rat and mouse pituitaries.

Age Factors↗