Thesis (Ph. D.)--University of Wisconsin--Madison, 1964. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Bibliography: leaves 135-142.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1959. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 124-136).

Literature concerning the structure and localisation of ACTH, MSI-1 and related peptides in mammalian pituitaries has been reviewed and the evidence for ACTH-like peptides in non-mammalian vertebrates summarised. The structure of ACTH in non-mammalian vertebrates was studied by bioassay and radioimmunoassay. Corticotrophin immunoreactivity in pituitary extracts from a variety of species was compared with that of natural human ACTH, using five antisera which cross-reacted with different parts of the ACTH molecule. The predominant binding sites of the antisera were determined by studies with synthetic ACTH fragments. Bioactivity and N-terminal immunoactivity were found in pituitary extracts of all species studies, Differences in reactivity with the C-terminally directed antisera indicated structural differences, between corticotrophins of the lower vertebrates, reptilian, avian and mammalian pituitary extracts cross-reacted with C-terminally directed, antisera. Whole reptile and mammal pituitaries were found to contain more C- than N-terminal activity. Determination of the relative concentrations of these activities in rat and guinea-pig pituitary lobes showed that the posterior lobes contained a large excess of C-terminal activity, which released into the media in organ culture. Fluorescent staining indicated that C-terminal activity was located in the pars intermedia. C-terminal immuno-active peptides were isolated from rat and pig pituitaries and a human tumour. On gel filtration they eluted between ACTH a-d a-MSH, and behaved as acidic peptides on ion-exchange chromatography. Amino acid and end group analysis showed that they closely resembled the alpha18-39 portion of ACTH. Consequently they have been termed 'Corticotrophin-like Intermediate lobe Peptide', (CLIP). The significance of the comparative studies with crude pituitary extracts of vertebrate origin and of the C-terminally immunoactive peptide isolated from rat, pig and human pituitaries has been discussed. The close resemblance of the latter to the C-terminal portion of ACTH, and of alpha-NSH to the N-terminal part of the ACTH molecule, suggest that alpha-NSH and the C-terminal peptide are the result of intracellular cleavage of ACTH. Implications of this mechanism have been considered.

The mouse AtT-20/D16-16 anterior pituitary tumour cell line was employed as a model system for the study of the mechanisms mediating calcium ion-stimulated adrenocorticotropin (ACTH) secretion. The present study indicates that calcium ion-stimulated ACTH secretion from AtT-20 cells is mediated by a GTP-binding protein which is present in a variety of other cell types and has been dubbed Ge (for reviews see Gomperts, 1990; Lindau & Gomperts, 1991). In AtT-20 cells the nature of Ge remains elusive with the selective heterotrimeric GTP-binding protein activator AIF(3-5) proving not to be a useful pharmacological tool under the conditions employed in the present study. Ge present in this cell line does however display characteristics consistent with it being a heterotrimeric GTP-binding protein. The results of this study would also suggest that in AtT-20 cells Ge is insensitive to both pertussis toxin and cholera toxin. Both cyclic AMP-dependent protein kinase (PKA) (Guild, 1991) and protein kinase C (PKC) (Guild & Reisine, 1987; Reisine, 1989) have been implicated in the regulation of calcium ion-stimulated ACTH secretion from AtT-20 cells. Results from the present study suggest that calcium ion/Ge-stimulated ACTH secretion from AtT-20 cells is not mediated by PKA, PKC or any other kinase but is in fact mediated by a phosphatase. PKC appears to provide a direct stimulus to secretion, which is independent of calcium ion/Ge-stimulated secretion, in contrast to PKA which is unable to stimulate secretion by itself but seems to play a modulatory role with regard to both calcium ion/Ge- and PKC-stimulated secretion.

FOXO1 is a forkhead transcription factor that inhibits proliferation and promotes apoptosis. It regulates genes that are involved in many diverse processes, including regulation of cell proliferation and cancer. The goal of our research is to understand FOXO1 and the role that it plays in human pituitary adenomas. Three objectives were outlined in this project to help determine the expression of FOXO1 in human pituitary adenomas. The first objective of this project was to analyze the spatial and temporal pattern of FOXO1 during mouse pituitary development. Objective one results showed that starting at e12.5, FOXO1 is cytoplasmic and becomes more nuclear later on in development. Immunohistochemical co-staining of FOXO1 and bromodeoxyuridine (BrdU) showed that FOXO1 does not co-localize with BrdU at e12.5, e14.5, and e16.5 showing that FOXO1 is not expressed in actively proliferating cells. The goal of objective two was to determine if expression levels of FOXO1 were abnormal in human pituitary adenomas. The results of objective two showed that when compared to FOXO1 expression in human normal pituitaries, FOXO1 was decreased in gonodotropinomas, null cell adenomas, and prolactinomas. In corticotropinomas, FOXO1 expression was increased while in somatotropinomas, FOXO1 expression was the same as compared in human normal pituitaries. Objective three was to assess whether spatial distribution of FOXO1 protein is abnormal in human pituitary tumor tissue. Our data showed that statistically there is no difference in FOXO1 spatial distribution between pituitary and normal samples. Overall, our real time RT-PCR data showed that FOXO1 expression is reduced in human gonadotropinomas, null cell adenomas, and prolactinomas. FOXO1 expression was increased in human cortiocotropinomas while it remained the same in human somatotropinomas. Immunohistochemistry staining revealed that statistically there was no difference in FOXO1 expression in the human pituitary samples when compared to human normal pituitary samples. These findings lead to the idea that loss of FOXO1 may help contribute to human pituitary tumorigenesis but more than likely other factors are involved.

No description available.

No description available.

No description available.

Goldfish were hypophysectomlzed and subsequently treated, with luteinizing, thyrotropic, adrenocorticotropic and lactotropic (prolactin) hormones; likewise some fish were treated with crude salmon pituitary extract. It was found that, hypophysectomized goldfish had a lower heat, resistance than normal fish, and that replacement therapy using these hormones produced no statistically significant effect on the heat resistance of hypophysectomized fish. Experiments were undertaken in which fish were subjected to either a long or short photoperiod. The results for the photoperiod manipulations were not always statistically significant at the 0.05 level, but there was always the suggestion that fish with intact pituitaries under the 16 hour photoperiod were more heat resistant than fish held under an 8 hour photoperiod. Experiments were carried out in which the pituitary was autotransplanted into the musculature of the caudal peduncle. Fish so treated had a heat resistance like that of pituitary intact 16 hour photoperiod fish while hypophysectomized fish had a heat resistance like that of pituitary intact 8 hour photoperiod fish. From a study of the endocrine (target) organs of these animals it is concluded that the autotransplanted pituitary secretes thyrotropic hormone in supernormal amounts, adrenocorticotropic hormone in subnormal amounts gonadotropic hormone not at all and prolactin in at least normal amounts. Based on information in the literature it seems that growth hormone is secreted in very small amounts by the transplanted pituitary. From all these experiments it is concluded that the pituitary is involved in heat resistance. It is suggested that it must be located in its normal position, for a photoperiod effect. By combining the histological information with the heat resistance results of the pituitary autotransplant experiments it is suggested that growth, gonadotropic, thyrotropic and adrenocorticotropic hormones play no major role in heat resistance. It is suggested that prolactin is the hormone most directly concerned with the heat resistance of goldfish; this hormone may also be involved in the photoperiod induced change in heat resistance. / Science, Faculty of / Zoology, Department of / Graduate