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Normal human pituitary gland and pituitary adenomas express cannabinoid receptor type 1 and synthesize endogenous cannabinoids: first evidence for a direct role of cannabinoids on hormone modulation at the human pituitary level.

Little is known about the expression and function of cannabinoid receptor type 1 (CB1) in the human pituitary gland. The aim of this study was to investigate CB1 expression in human normal and tumoral pituitaries by in situ hybridization and immunohistochemistry using an antibody against CB1. CB1 was found in corticotrophs, mammotrophs, somatotrophs, and folliculostellate cells in the anterior lobe of normal pituitary. After examination of 42 pituitary adenomas, CB1 was detected in acromegaly-associated pituitary adenomas, Cushing's adenomas, and prolactinomas, whereas faint or no expression was found in nonfunctioning pituitary adenomas. Experiments with cultured pituitary adenoma cells showed that the CB1 agonist WIN 55,212--2 inhibited GH secretion in most of acromegaly-associated pituitary adenomas tested and that the CB1 antagonist SR 141716A was generally able to reverse this effect. Moreover, WIN 55,212--2 was able to suppress GHRH-stimulated GH release, and this effect was not blocked by coincubation with SR 141716A, possibly indicating a non-CB1-mediated effect. In contrast, WIN 55,212--2 was ineffective on GH-releasing peptide-stimulated GH release. In four Cushing's adenomas tested, WIN 55,212--2 was not able to modify basal ACTH secretion. However, simultaneous application of CRF and WIN 55,212--2 resulted in a synergistic effect on ACTH secretion, and this effect could be abolished by SR 141716A, demonstrating a CB1-mediated effect. In the single case of prolactinomas tested, WIN 55,212--2 was able to inhibit basal secretion of PRL. Finally, the presence of endocannabinoids (anandamide and 2-arachidonoylglycerol) was investigated in normal and tumoral pituitaries. All tumoral samples had higher contents of anandamide and 2-arachidonoylglycerol compared with the normal hypophysis. Moreover, endocannabinoid content in the different pituitary adenomas correlated with the presence of CB1, being elevated in the tumoral samples positive for CB1 and lower in the samples in which no or low levels of CB1 were found. The results of this study point to a direct role of cannabinoids in the regulation of human pituitary hormone secretion.

Adenoma↗

Is technetium-99m-MIBI taken up by the normal pituitary gland? A comparison of normal pituitary glands and pituitary adenomas.

PURPOSE: The aim of this study was to compare the behavioral uptake of a normal gland and a pituitary adenoma and to assess the ability to diagnose pituitary adenoma by means of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (MIBI) single photon emission computed tomography (SPECT). METHODS: The study included 15 patients with pituitary adenomas (mean age = 44.0 years, range 19-63) and 15 control subjects (mean age = 50.7 years, range 20-67). SPECT was performed 15 minutes after an intravenous injection of MIBI 600 MBq. The shape and location of MIBI uptake were evaluated on a magnetic resonance (MR) imaging/SPECT registration image. The shape patterns and location were classified as follows: Shape C (circular); LO (longitudinal oval); T/R (triangular or rectangular) and location P (pituitary gland or adenoma); D/C (dorsum sellae and/or clivus). RESULTS: Analysis of the uptake showed that 10 (67%) adenomas were C, and 5 (33%) were LO. Of the controls, 5 (33%) were C, and 10 (69%) were T/R. With regard to location, all patients with pituitary adenomas were classified as P, and all control subjects (93%) but one showed uptake in the dorsum sellae and clivus (D/C). CONCLUSION: MIBI was taken up in the dorsum sellae or clivus but not the normal pituitary gland and had a strong affinity for the pituitary adenoma. This result implies that MIBI SPECT may be a useful new auxiliary examination technique for the location diagnosis of pituitary adenoma.

Adenoma↗

[Effect of veralipride on the estral cycle, genital tract, mammary gland and pituitary gland in female rats (author's transl)].

A study of the potential biological effects of veralipride was conducted in female rats. A definite stimulating action on the mammary gland was noted, but doses of 5 to 20 mg/kg/day are required to produce secretion, which is varying from one animal to another. Follicular maturation is preserved, though there is an increase in the number of corpora lutea with more marked development in some of them. Progesterone impregnation of the uterus occurs in a variable way and then only at doses of 5 + 0 20 mg/kg/day. Vaginal mucification, from a reduction in estrogen in relation to progesterone impregnation, is noted after 1 mg/kg/day (though 25 p. cent of the animals still demonstrate vaginal keratinization after 20 mg/kg/day). Finally, degranulation of the carminophile cells of the anterior pituitary gland, occurs after 5 mg/kg/day.

Animals↗

Pheromone-induced changes in the acidophil concentration of mouse pituitary glands.

Pituitaries of female mice in anestrus resulting from colony housing were characterized by a 58.0-percent (acidophil content. Subsequent exposure to restrained male mice for one and two nights failed to evoke significant acidophilic degranulation and resulted in pituitary acidophil values of 57.4 and 55.1 percent respectively. Exposure to released males on the third night produced marked acidophilic degranulation resulting in a significant decline in pituitary acidophils to 38.0 percent. These findings support the view that female pheromone suppresses and male pheromone favors the secretion of follicle-stimulating hormone and indicate that luteotrophic hormone is secreted at its assigned time in the sequence of cyclic ovarian events initiated by the secretion of follicle-stimulating hormone.

Animals↗

[Allometry and linear correlation coefficients binding the volumes of the different pituitary gland lobes, of the pituitary gland, of the subfornical organ and of the pineal gland to body weight and to hypothalamic volume in Rodents and in a Lagomorphe].

The morphometric study of the hypophysis, of the subfornical organ and of the pineal gland of 41 Rodents and one Lagomorphe shows that the anterior lobe of the hypophysis as well as the total hypophysis are better correlated to body weight than to the volume of the hypothalamus, while it is the contrary for the pars nervosa. The volume of the intermediate lobe varies very much from one species to another for the same body weight. The high value of the allometry coefficient of the pineal gland on somatic weight (1.25) is due to the fact that the heavy Rodents of our temperate climates have a large epiphysis while the small african Rodents possess a small pineal gland.

Animals↗

Immunohistochemical analyses of thyroid-specific enhancer-binding protein in the fetal and adult rat hypothalami and pituitary glands.

Thyroid-specific enhancer-binding protein (T/EBP), also known as NKX2.1 or TTF-1, regulates the expression of thyroid- and lung-specific genes. The t/ebp/Nkx2.1-null mutant mouse was stillborn but lacked the thyroid gland, pituitary gland, ventral region of the forebrain and normal lungs. These data demonstrated that T/EBP/NKX2.1 plays an important role not only in tissue-specific gene expressions in adults but also in genesis of these organs during development. Although the expression of t/ebp/Nkx2.1 in the brain has been reported, its function in the brain remains unknown. The present study was designed to determine the localization of T/EBP/NKX2.1 in the hypothalamus and pituitary gland of fetal and adult rats by immunohistochemistry as the first step toward understanding the function of T/EBP/NKX2.1 in the rat brain. In the fetal rat hypothalamus, T/EBP/NKX2.1 was localized widely in the ventral hypothalamic areas. In the adult rat brain, T/EBP/NKX2.1 was localized in the ventromedial hypothalamic nucleus, medial tuberal nucleus, arcuate nucleus and mammillary body. No T/EBP/NKX2.1 immunoreactivity was observed in the anterior or intermediate lobe of the pituitary gland in either fetal or adult rats. On the other hand, immunoreactive T/EBP/NKX2.1 was found in the posterior lobe of the pituitary gland. This paper presents results of detailed analyses of the distributions of T/EBP/NKX2.1 protein in the fetal and adult rat hypothalami and pituitary glands, and these results should provide important information for understanding the function of T/EBP/NKX2.1 in the brain.

Age Factors↗

cDNA cloning and mRNA expression analysis of the human neuronatin. High level expression in human pituitary gland and pituitary adenomas.

The authors cloned the nearly complete cDNA of human neuronatin with the aid of an expressed sequence tag (EST) database, and analyzed its expression in various human tissues by Northern blot analysis. The nucleotide and deduced amino acid sequences of the human neuronatin showed a high similarity to those of rodents. The Northern blot analysis revealed that the human neuronatin message was expressed predominantly in the fetal brain in the brain-specific manner, but only faintly in the adult brain. Among the various adult human tissues examined, the anterior pituitary gland was shown to be the only place where the neuronatin mRNA was strongly expressed. Intense neuronatin expression was also observed in several human pituitary adenomas, including ACTH-producing, GH-producing, and nonfunctioning adenomas, but hardly detected in other brain tumors.

Adenoma↗

Sequential MR enhancement pattern in normal pituitary gland and in pituitary adenoma.

PURPOSE: To measure and evaluate the temporal enhancement characteristics of the normal pituitary gland and pituitary adenoma. METHODS: Thirty healthy subjects and 10 patients with sellar pituitary adenomas were studied prospectively using dynamic MR imaging with a 5- or 10-sec temporal resolution during a bolus injection of gadolinium. RESULTS: Qualitative visual analysis demonstrated a consistent sequential pattern of pituitary enhancement in which the posterior lobe enhanced earlier than the anterior lobe by approximately 35 sec. Quantitative analysis revealed that posterior lobe enhancement occurred 9.8 +/- 1.5 sec (mean +/- SEM) before the anterior lobe in healthy subjects, whereas tumor enhancement occurred significantly before the anterior lobe but only slightly before the posterior lobe in patients with adenomas. CONCLUSION: The sequential enhancement pattern of the normal pituitary gland was found to be consistent with its vascular anatomy. In contrast to previous reports, pituitary adenomas were found to enhance earlier than the anterior lobe. These results suggest that pituitary adenomas have a direct arterial blood supply, similar to that of the posterior pituitary lobe.

Adenoma↗

Immunohistochemical demonstration of cytokeratins in endocrine cells of the human pituitary gland and in pituitary adenomas.

Ten non-neoplastic pituitary glands and 22 pituitary adenomas producing different hormones were studied by immunofluorescence microscopy as well as peroxidase-antiperoxidase and biotin-avidin techniques on frozen sections and formalin-fixed, paraffin-embedded material using antibodies to cytokeratin, vimentin, GFAP, neurofilament protein and different pituitary hormones. The endocrine cells in non-neoplastic pituitary glands as well as in most pituitary adenomas were cytokeratin-positive. The cytoplasmic cytokeratin distribution patterns of non-neoplastic and tumor cells were similar and typical of the type of hormone produced: GH-producing normal cells showed a paranuclear condensation of cytokeratin-reactive intermediate filaments; this accumulation was even further accentuated in GH-producing adenomas resulting in fibrous bodies (Kovacs and Horvath 1978) decorated by cytokeratin antibodies. Prolactin-producing cells showed a less intense cytoplasmic cytokeratin-specific staining with focal paranuclear accentuation in non-neoplastic as well as in neoplastic glands. ACTH-producing cells in normal pituitary glands as well as in adenomas exhibited a strong and more uniform cytoplasmic cytokeratin staining. The cytokeratin reactivity in glycoprotein hormone-producing cells of non-neoplastic tissue and adenomas was weak. Vimentin and GFAP reactivity was confined to agranular folliculo-stellate cells. The specific and different distribution patterns of cytokeratins in pituitary cells can, therefore, provide an (indirect) indication to the production of a specific hormone if immunocytochemistry fails to demonstrate hormone production.

Adenoma↗

Levels of alpha-melanotrophin in the human fetal pituitary gland throughout gestation, in adult pituitary gland and in human placenta.

alpha-Melanotrophin was detected by radioimmunoassay in the human fetal pituitary gland from 11 weeks of gestation. The peak hormone concentration of 3.4 nmol/g pituitary tissue was reached at 17-20 weeks. From 17 to 36 weeks of gestation the total gland content rose gradually from 28 to 102 pmol. During this latter period, the pituitary gland grew some 10-fold, with the result that the alpha-melanotrophin concentration declined steadily to 1.3 nmol/g. In the final month of gestation, both the total gland content and the concentration of alpha-melanotrophin rose significantly to 254 pmol and 2.4 nmol/g respectively. The variations in pituitary gland content of alpha-melanotrophin were consistent with a role for pars intermedia peptides in the fetus. alpha-Melanotrophin-like peptides were not demonstrated in human placental tissue.

Adult↗

The corticotrophic cells of the canine pituitary gland in pituitary-dependent hyperadrenocorticism.

The distribution of specifically stained corticotrophic cells has been studied in the pituitary glands of 11 dogs with pituitary-dependent hyperadrenocorticism. The results suggest that the disease is not a single entity, and that some cases are caused by primary abnormality of the pituitary gland whereas others appear to be the result of dysfunction of the hypothalamus or central nervous system. The patterns correspond closely to those demonstrated in the human pituitary gland in Cushing's disease, and confirm that the canine disease is a useful model for the study of the pathogenesis of the variants of the condition.

Adrenocorticotropic Hormone↗

Microsurgical anatomy of the pituitary gland and the sellar region. 1. The pituitary gland.

The microsurgical anatomy of the pituitary gland was studied on dissections of 250 cadaver sphenoidal blocks and on detailed operative reports of 266 patients who underwent transsphenoidal hypophysectomy (185 breast cancer patients and 81 patients with diabetic retinopathy). Whereas the various measurements (width, length, height, weight) and the structures of the two lobes of the pituitary gland were studied in cadavers, texture, consistency, color, and attachment to surrounding structures were best observed during surgical procedures. These latter aspects of the pituitary gland were correlated with the age, sex, and hormonal status of the patients. Variations in the shape, size, and appearance of the pituitary gland are frequent. Knowledge of such variations is important for a precise microsurgical approach to the sellar region.

Adult↗

Growth patterns of the normal pituitary gland and in pituitary adenoma.

The growth pattern of the pituitary gland of 86 infants, children and adolescents without pituitary or hypothalamic dysfunction was studied with sagittal magnetic resonance imaging. Postnatally the gland grew rapidly, reaching a plateau at almost three years after birth, and growing rapidly again between the age of 10 to 13 years. Pituitary gland area showed a similar growth pattern to gland height. The pituitary glands of seven patients with pituitary adenomata were also examined. All had convex upper-gland margins, with height and area significantly greater than those of normal controls of the same age.

Adenoma↗