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, 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.

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

The activity of the pituitary-interrenal axis in juvenile coho salmon (Oncorhynchus kisutch) and the relationship of this activity to the numbers of circulating leucocytes has been studied, using histological and histometric techniques. To this end, the effects of injections of mammalian ACTH, of Cortisol acetate and of dexamethasone on the interrenal tissue, on the epsilon cells in the pituitary gland, and on the differential leucocyte counts were investigated. In addition, the activity of the pituitary-interrenal axis and the related changes in leucocyte counts were determined throughout their year of stream residence. Further, the response of this axis, along with corresponding hematological changes to environmental alterations in the laboratory, were studied. Injections of ACTH resulted in a dosage-related stimulation of the interrenal tissue of coho salmon fry. On the other hand, injections of Cortisol acetate and of dexamethasone produced a marked atrophy of the interrenal tissue. All dosages of either ACTH or Cortisol acetate decreased the mean nuclear diameters of epsilon cells, and resulted in their degranulation. In addition, a decrease in numbers of circulating small lymphocytes and thrombocytes resulted from administration of all dosages of ACTH, Cortisol acetate or dexamethasone. It is proposed that the interrenal tissue of coho fry is capable of marked variations in activity, that this tissue is under pituitary control, and that a negative-feedback mechanism operates between the interrenal and the pituitary gland. Additionally, changes in pituitary-adrenocortical activity are reflected in characteristic alterations in numbers of certain circulating leucocytes. The pituitary-interrenal axis of juvenile coho salmon in their natural habitat is inactive, from the time of emergence in spring, and through summer and early fall, compared with the winter and spring samples of yearling coho. In addition, numbers of circulating small lymphocytes were decreased in the winter and spring samples of yearling coho compared with summer and autumn samples. It is suggested that the increased activity of the pituitary-interrenal axis along with changes in leucocyte counts observed in the winter sample of juvenile coho salmon are related to cold-temperature acclimation. Furthermore, it is proposed that the increased pituitary-adrenocortical activity noted in the latest of the three spring samples of yearling coho salmon is associated with the transformation from parr to smolt. The interrenal tissue of juvenile coho salmon maintained in continuous darkness, or exposed to a continuously flashing light for varying numbers of days, was generally more active than that of corresponding control fish subjected to a twelve hour photoperiod. Additionally, small-lymphocyte and thrombocyte counts for darkness-maintained and flash-exposed fish were lower than values for corresponding control samples. On the other hand, no consistent differences in activity of the interrenal tissue were found when fish maintained in continuous light for varying numbers of days and corresponding control fish were compared. It was observed that the pituitary-interrenal axis of juvenile coho salmon was initially stimulated following transfer of the fish from holding tanks to an altered environment. In addition, the activity of the interrenal tissue was increased by exposure of these fish to cold water temperatures; this increased interrenal activity was accompanied by a lymphopenia. It is suggested that the pituitary-interrenal axis of juvenile coho salmon is involved in cold-temperature acclimation. It is concluded that the pituitary-interrenal axis of juvenile coho salmon undergoes marked fluctuations in activity as a result of environmental alterations within the laboratory. Furthermore, an increase in pituitary-adrenocortical activity during acclimatization is characteristically reflected in a decrease in number of.circulating small lymphocytes. / Science, Faculty of / Zoology, Department of / Graduate

No description available.

No description available.