ABSTRACT
The gene apparently responsible for a heritable form of murine pituitary-dependent dwarfism (Ames dwarf, df) has been positionally cloned, identifying a novel, tissue-specific, paired-like homeodomain transcription factor, termed Prophet of Pit-1 (Prop-1). The df phenotype results from an apparent failure of initial determination of the Pit-1 lineage required for production of growth hormone, prolactin or thyroid-stimulating hormone, resulting in dysmorphogenesis and failure to activate Pit-1 gene expression. These results imply that a cascade of tissue-specific regulators is responsible for the determination and differentiation of specific cell lineages in pituitary organogenesis.
Subject(s)
DNA-Binding Proteins/genetics , Dwarfism, Pituitary/genetics , Homeodomain Proteins/genetics , Pituitary Gland, Anterior/embryology , Transcription Factors/genetics , Alleles , Amino Acid Sequence , Animals , Cell Lineage , Dwarfism, Pituitary/embryology , Female , Gene Expression , Homeodomain Proteins/physiology , Hypothalamus/physiology , Male , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Pituitary Gland, Anterior/abnormalities , Pituitary Gland, Anterior/physiology , Point Mutation , Sequence Homology, Amino Acid , Signal Transduction , Transcription Factor Pit-1ABSTRACT
In the pars distalis of the pituitary gland in adult and embryonic dwarf (dw/dw) mutant mice, ambiguous cells exhibiting ultrastructural features common to growth hormone (GH) cells and prolactin (Prl) cells were analyzed by means of colloidal gold ultrastructural immunocytochemistry in order to define the functional nature of these peculiar cells. Adult and 18-day embryonic pituitaries from normal (+/+; dw/+) and dwarf (dw/dw) mice were processed with antibodies to GH, Prl, TSH (thyroid-stimulating hormone), ACTH (adrenocorticotropic hormone), LH (luteinizing hormone), FSH (follicle-stimulating hormone), and HCG (chorionic gonadotropic hormone). In the adult and embryonic dwarf pituitaries, the ambiguous cells reacted negatively to all of the antibodies except for anti-ACTH, which labeled them well. In addition, the ACTH-positive cells showed a much wider variety of shapes and granule size and distribution, as compared with normal adults. In the embryos, this variability in ACTH cell morphology occurred not only in dwarf embryos, but in their normal counterparts as well. The results thus suggest that adult dwarf pituitaries may retain an embryonic or incompletely differentiated form of ACTH cells.
Subject(s)
Adrenocorticotropic Hormone/analysis , Dwarfism, Pituitary/pathology , Mice, Mutant Strains , Pituitary Gland, Posterior/pathology , Animals , Dwarfism, Pituitary/embryology , Dwarfism, Pituitary/genetics , Female , Immunohistochemistry , Male , Mice , Mice, Mutant Strains/genetics , Microscopy, Electron , Pituitary Gland, Posterior/chemistry , Pituitary Gland, Posterior/embryologyABSTRACT
Magnetic Resonance (MR) imaging was carried out on 33 patients with idiopathic growth hormone deficiency, in 22 of whom CT scan had been carried-out previously. Twenty-one patients presented some complications at birth. Both MR and CT were positive in the evaluation of the sella. MR imaging exhibited a higher degree of accuracy than CT in the evaluation of pituitary gland, pituitary stalk and brain anomalies. On the basis of pituitary morphology demonstrated by MR imaging, and perinatal histories, a classification is proposed which divides our patients into three group: A) a first group of 13 patients presenting severe hypoplasia of the anterior pituitary lobe, hypoplasia of the stalk and ectopia of posterior lobe. The underlying cause of these anatomic defects might be developmental in origin, and date from early intrauterine life, probably worsened at birth. B) a second group of 10 patients presenting severe hypoplasia of the anterior pituitary lobe. A perinatal event and birth trauma might be responsible for pituitary damage. C) a third group of 10 patients with no morphological abnormalities of the pituitary gland. A derangement of the neuroendocrine mechanism which control the growth hormone secretion might account for these patients.
Subject(s)
Brain/diagnostic imaging , Brain/pathology , Dwarfism, Pituitary/diagnosis , Magnetic Resonance Imaging , Pituitary Gland/diagnostic imaging , Pituitary Gland/pathology , Tomography, X-Ray Computed , Adolescent , Child , Dwarfism, Pituitary/embryology , Dwarfism, Pituitary/etiology , Female , Humans , Magnetic Resonance Imaging/economics , Male , Sex Factors , SyndromeABSTRACT
Blood vessels in the pars distalis of the embryonic pituitary gland of the dwarf (dw) mutant mouse were analyzed by means of electron microscopy. Dwarf (dw/dw) embryos ranging in age from 15 through 18 days of gestation were obtained from matings of dwarf homozygotes in which reproductivity was induced by means of hormone supplementation and grafts of normal pituitary to the kidney capsule. Endothelial cells in vessels of the dwarf pituitary were retarded in development as indicated by a retention of macrovesicles and marginal flaps beyond embryonic stages when they normally subside in normal embryos, as well as a lag in the development of endothelial cell attenuations. This retardation may be causally related to the pituitary pathology involving faulty cytodifferentiation of somatotrophs and mammotrophs.
