Topographical distribution of the gonadotrophs,mammotrophs, somatotrophs and thyrotrophs in the pituitary gland of the baboon (Papio cynocephalus)

The identification and regionalization of four pituitary parenchymal cell types, gonadotrophs, mammotrophs, somatotrophs and thyrotrophs, were studied in the baboon (Papio cynocephalus) hypophysis using immunocytochemistry. The gonadotrophs were homogeneously distributed throughout the entire pars distalis. Both mammotrophs and somatotrophs predominate at the superior and inferior poles of the organ. The medial and anteromedial regions are populated by mammotrophs and thyrotrophs, while the lateral and posterior portions of the pars distalis contain large numbers of somatotrophs.     

Effect of thyroid hormone and sex status on epidermal growth factor concentrations in the submandibular gland of a congenitally hypothyroid mouse model

Studies were performed to explore the role of thyroid hormone and sex status on epidermal growth factor concentrations in the submandibular gland of a congenitally hypothyroid mouse model designated hyt/hyt. The animals were studied at 20, 30 and 40 days of postnatal age. The euthyroid animals were homozygous or heterozygous for the hypothyroid gene. The homozygous euthyroid animals displayed a pattern of submandibular gland epidermal growth factor concentrations similar to those previously described in other mouse species and showed the expected sex differences. The hypothyroid animals had measurable but very low submandibular gland epidermal growth factor concentrations without sexual dimorphism. Serum thyroxine concentrations in the heterozygotes were comparable to those in the homozygous euthyroid animals, yet the animals had a delayed increase in epidermal growth factor concentrations combined with a later expression of female-male differences. The timing of the sex differences in submandibular gland epidermal growth factor concentrations followed a pattern similar to that seen for the timing of the first litter in these three genetically distinct groups. This infers the timing of the onset of puberty and suggests a role of androgens in the changes seen in epidermal growth factor concentrations. We conclude that thyroid hormone and sex status in this mouse model influence the pattern and concentrations of submandibular gland epidermal growth factor concentrations.     

Requirement of thyrotropin-releasing hormone for the postnatal functions of pituitary thyrotrophs: ontogeny study of congenital tertiary hypothyroidism in mice

We recently reported that TRH-deficient mice showed characteristic tertiary hypothyroidism. In the present study, we investigated how this tertiary hypothyroidism occurred particularly in pre- and postnatal stages. Immunohistochemical analysis revealed a number of TSH-immunopositive cells in the TRH-/- pituitary on embryonic day 17.5 and at birth. The mutant pituitary at birth in pups born from TRH-deficient dams also showed no apparent morphological changes, indicating no requirement of either maternal or embryonic TRH for the development of pituitary thyrotrophs. In contrast, apparent decreases in number and level of staining of TSH-immunopositive cells were observed after postnatal day 10 in mutant pituitary. Similar decreases were observed in the 8-week-old mutant pituitary, while no apparent changes were observed in other pituitary hormone-producing cells, and prolonged TRH administration completely reversed this effect. Consistent with these morphological results, TRH-/- mice showed normal thyroid hormone levels at birth, but the subsequent postnatal increase was depressed, resulting in hypothyroidism. As expected, TSH content in the TRH-/- pituitary showed a marked reduction to only 40% of that in the wild type. Despite hypothyroidism in the mutant mice, both the pituitary TSHbeta and alpha mRNA levels were lower than those of the wild-type pituitary. These phenotypic changes were specific to the pituitary thyrotrophs. These findings indicated that 1) TRH is essential only for the postnatal maintenance of the normal function of pituitary thyrotrophs, including the normal feedback regulation of the TSH gene by thyroid hormone; 2) neither maternal nor embryonic TRH is required for normal development of the fetal pituitary thyrotroph; and 3) TRH-deficient mice do not exhibit hypothyroidism at birth. Moreover, reflecting its name, TRH has more critical effects on the pituitary thyrotrophs than on other pituitary hormone-producing cells.     

The fertility of hypothyroid male mice

Male mice homozygous for the hypothyroid gene mutation were compared with normal siblings to determine whether hypothyroidism induced infertility by impairing sexual behaviour. In addition, the fertility of the hypothyroid mice was examined. The experimental results provide unequivocal evidence that genetically-induced hypothyroidism in male mice does not impair sexual behaviour or cause infertility.     

Demonstration of pineal gland and pituitary involution in mice poisoned with carbon tetrachloride]

Ingestion of carbone tetrachloride by male C3H Orleans mice determines an involution of the pineal gland and of the hypophysis, as well as extensive lesions of the hepatic parenchyma. There may exist in these animals a higher blood-level of glucocorticoids, as this has been shown to be the case in men suffering from cirrhosis or hepatitis. Involution of the pineal gland in cases of stress, as has been shown by various authors, would result from an entirely different mechanism, that is by increased secretion of corticoadrenal hormones.     

Histopathology of the pituitary gland in neonatal little (lit) mutant mice.

The pituitary gland in the little (lit) mutant mouse was analyzed with respect to the cytoarchitecture of the pars distalis and the volumetric density of immunoreactive growth hormone (GH) cell granules in neonatal lit/lit and normal C57BL mice. At 8 days postnatally the volume of GH granules/total tissue was significantly less in the lit/lit pars distalis, and the cells were loosely arranged, as compared with the normal pars distalis. In newborn mice a statistically significant difference could not be detected between normal and lit/lit mice with respect to the volumetric density of GH granules; however, differences occurred in the cytoarchitectural organization of the pars distalis. These differences included prominent vascular channels and well-defined cords and clusters of cells in the normal newborn mice, in contrast to indistinct vascular elements and a more diffuse arrangement of cells in lit/lit.     

A pituitary-salivary mixed gland induced by tissue recombination of embryonic pituitary epithelium and embryonic submandibular gland mesenchyme in mice

Renal subcapsular syngrafts of Day 9 to 11 mouse embryonic pituitary epithelium with Day 14 mouse embryonic submandibular gland mesenchyme produced mixed organs that include residual cleft structure surrounded by anterior pituitary cells some which are stained by anti-ACTH antiserum and submandibular gland-like structure with differentiated acinar cells which are stained by anti-alpha-amylase antiserum. However, when Day 8.5 or 12 embryonic pituitary epithelium was recombined with submandibular gland mesenchyme and syngrafted, development of submandibular gland-like or anterior pituitary tissues resulted, respectively. Thus, during organogenesis of the mouse anterior pituitary, there exists a developmental stage (Day 8.5-11 in utero), when prospective pituitary epithelium can respond to heterotypic submandibular gland mesenchyme with the development of a submandibular gland-like tissue.     

Cre-mediated recombination in the pituitary gland

Organ-specific expression of a cre recombinase transgene allows for the analysis of gene function in a particular tissue or cell type. Using a 4.6 kb promoter from the mouse glycoprotein hormone alpha-subunit (alphaGSU or Cga) gene, we have generated and characterized a line of transgenic mice that express cre recombinase in the anterior and intermediate lobes of the pituitary gland. Utilizing a cre-responsive reporter transgene, alphaGSU-cre transgene expression was detected in the pituitary primordium and in all five cell types of the adult anterior pituitary. alphaGSU-cre transgene activity was also detected in the cardiac and skeletal muscle. Little or no activity was evident in the gonads, adrenal glands, brain, ventromedial hypothalamus, or kidneys. The alphaGSU-cre transgenic mice characterized here will be a valuable tool for examining gene function in the pituitary gland.     

Experimental mucormycosis in congenitally athymic (nude) mice

Athymic nude (nu/nu) mice and their phenotypically normal (nu/+) littermates displayed a similar susceptibility to acute lethal infection withAbsidia corymbifera. Although the clinical manifestations of acute infection were also similar in both groups, the nude mice tended to develop more extensive lesions and were less effective in eliminating viableA. corymbifera spores than their heterozygous littermates. The results suggested that thymus-dependent processes did not play an essential role in primary resistance to mucormycosis.     

Tumors induced by 1,2-dimethylhydrazine in hybrid mice with the pituitary gland transplanted in the kidney

1,2-Dimethylhydrazine (DMH) decreased the incidence of tumors in hypophyseal isografts in hybrid mice (CBA X C57BL/6)F1 and prevented the development of mammary tumors. In mice bearing hypophyseal isografts, there was a decrease in the incidence of DMH-induced hemangiomas of the ovary. The same mice showed no alterations in the incidence of DMH-induced uterine sarcomas, tumors of the large intestine, anal region and liver.     

Immunohistochemical study of the postnatal development of pituitary thyrotrophs in the rat,with special reference to cluster formation

Summary The postnatal development of rat pituitary thyrotrophs was investigated immunohistochemically on days 1, 3, 5, 10, 15 and 25. Fetal thyrotrophs are strongly immunoreactive. In the postnatal period, however, weakly immunoreactive thyrotrophs increase in number to constitute clusters on days 3–5. The numbers and dimensions of the clusters reach a maximum on day 10. Thereafter the clusters break down to give rise to single, scattered neogenic thyrotrophs. Thyrotrophs in clusters on day 10 were investigated by electron microscopy in adjacent sections. They can be characterized as an immature type of basophil, according to the classification of Yoshimura et al. (1977): 1) Type I basophils, which are irregularly shaped with elongate processes, and characterized by rows of secretory granules about 100 nm in diameter. 2) Type I/II basophils, i.e., forms intermediate between Types I and II, containing less numerous secretory granules about 100–150 nm in diameter. Type II basophils which correspond to the classical thyrotrophs are not fully developed on day 10. Thus, most thyrotrophs develop from the clusters in the neonatal period. Such neogenic thyrotrophs retain the immature characteristics of Type I and I/II cells and may develop into Type II cells during subsequent maturation.     

Making a pituitary gland in a dish

The adenohypophysis secretes multiple hormones that control vital physiological functions. A recent article in Nature (Suga et al., 2011) describes a 3D protocol for the derivation of several endocrine pituitary cell types from mouse ESCs.