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

Some three years ago I availed myself of an opportunity of pursuing a research project in the Department of Medicine at this Medical School. At that time, a long established interest in the study of plasma albumin metabolism was given fresh impetus by the development of techniques which overcame the problem of measuring rates of albumin synthesis and catabolism under conditions of metabolic chonge. Interest in the Department had centred mainly upon the nature of the adaptive changes occurring in albumin metabolism in response to altered dietary protein intake, and by the time I was due to take up my appointment many of these adaptive changes had been clearly defined. The factors mediating these changes however remained unknown.

Some three years ago I availed myself of an opportunity of pursuing a research project in the Department of Medicine at this Medical School. At that time, a long established interest in the study of plasma albumin metabolism was given fresh impetus by the development of techniques which overcame the problem of measuring rates of albumin synthesis and catabolism under conditions of metabolic chonge. Interest in the Department had centred mainly upon the nature of the adaptive changes occurring in albumin metabolism in response to altered dietary protein intake, and by the time I was due to take up my appointment many of these adaptive changes had been clearly defined. The factors mediating these changes however remained unknown.

No description available.

Gonadotropin-releasing hormone (GnRH) and its superactive analogues are currently being used in the treatment of a number of endocrine disorders, such as endometriosis, precocious puberty, infertility and prostatic cancer. Selection of these analogues for clinical use have been previously based on their activities in animal models. This thesis has therefore investigated the binding characteristics of the human GnRH receptor, in comparison to those of the rat receptor, as well as the activities of a number of GnRH analogues for stimulating luteinising hormone (LH) and follicle stimulating hormone (FSH) secretion from cultured human pituitary cells. The establishment of a human pituitary bioassay system has further made possible the investigation of the direct regulatory roles of GnRH and other neuropeptides in man. To date, such studies in man have been performed in vivo and are thus complicated by the simultaneous interactions of numerous modulators.

To test the hypothesis that the hypothalamic tuberoinfundibular dopaminergic neuronal system plays a role in the dynamic regulation of pituitary prolactin secretion, its activity was correlated with experimentally-induced prolactin secretory episodes in the male rat. Direct estimates of tuberoinfundibular neuronal activity were made by measuring its rates of dopamine and norepinephrine synthesis or release. Prolactin secretion was assessed in vivo by measuring radioimmunoassayable prolactin levels in peripheral blood and the pituitary and in vitro by measuring prolactin concentrations released into incubation media. The anesthetic urethane and a substance isolated from the pineal gland were both demonstrated to inhibit prolactin secretion. Significant elevations of newly synthesized tuberoinfundibular dopamine were observed concomitant with this decreased prolactin secretion suggesting that acute increases in tuberoinfundibular dopaminergic neuronal activity were perhaps causally related to acute decreases in prolactin secretion since these substances were without a direct effect on the pituitary in vitro. Conversely, acute decreases in tuberoinfundibular neuronal activity induced by dopamine biosynthesis inhibition or mimicked by pituitary receptor blockade induced acute increases in prolactin secretion. As another prerequisite for its involvement in the dynamic regulation of prolactin secretion, the tuberoinfundibular neuronal system was demonstrated to be involved in the negative feedback control of prolactin over its own secretion. Elevated circulating prolactin levels produced by pituitary homografts transplanted beneath the kidney capsule accelerated tuberoinfundibular dopaminergic neuronal activity. In two unrelated experimental conditions, rats rendered blind and anosmic or hyperprolactinemic, the chronic inhibition of prolactin secretion was not associated with the maintenance of an increased tuberoinfundibular neuronal activity, but rather with a supersensitivity of the anterior pituitary to the prolactin-release-inhibitory action of dopamine. Long-lasting alterations in tuberoinfundibular dopaminergic neuronal activity appeared to induce this pituitary supersensitivity to dopamine. The tuberoinfundibular neuronal system appears to have the capacity to modulate prolactin secretory episodes via the alteration of its dopaminergic activity. Long-lasting alterations in this activity may induce changes in anterior pituitary sensitivity to dopamine essential for the chronic inhibition of pituitary prolactin secretion.

No description available.

Prenatal ethanol (E) exposure has marked effects on development of the hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes. E rats show HPA hyperresponsiveness to stressors and altered reproductive function in adulthood. Importantly, prenatal ethanol differentially alters stress responsiveness in adult males and females, raising the possibility that gonadal hormones play a role in mediating ethanol effects on HPA function. To address this possibility, two studies were conducted to test the hypothesis that the differential alterations in HPA activity observed in E compared to control males are mediated, at least in part, by ethanol-induced changes in HPG effects on HPA regulation. The first study compared the effects of gonadectomy (GDX) on HPA and HPG activity in adult male offspring from prenatal E, pair-fed (PF) and ad libitum-fed control (C) dams. There were no differences among groups in basal testosterone levels under intact conditions. However, E males showed increased adrenocorticotropin but blunted testosterone and luteinizing hormone (LH) responses to restraint stress compared to PF and/or C rats, and no stress-induced elevation in arginine vasopressin (AVP) mRNA levels. GDX eliminated these differences among groups. The second study explored dose-related effects of testosterone on HPA regulation. Testosterone had less of an inhibitory effect on stress-induced CORT and LH increases in E than in PF and C males. Furthermore, testosterone had a reduced effect on central corticotropin-releasing hormone pathways, but an increased effect on central AVP pathways in E compared to PF and/or C males. Importantly, reduced androgen receptor (AR) mRNA levels, possibly reflecting downregulation of AR in key brain areas, may counteract the increased inhibitory AVP signals upstream from the paraventricular nucleus, and thus contribute to the HPA hyperresponsiveness seen in E males. Together these findings suggest that central regulation of both the HPA and HPG axes are altered by prenatal ethanol exposure. The capacity of testosterone to regulate HPA activity is altered in E males, with some effects mediated by the nutritional effects of ethanol. These changes would impair the ability to maintain homeostasis in E animals and have implications for the development of secondary disabilities in children with Fetal Alcohol Spectrum Disorder.

Prenatal ethanol (E) exposure has marked effects on development of the hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes. E rats show HPA hyperresponsiveness to stressors and altered reproductive function in adulthood. Importantly, prenatal ethanol differentially alters stress responsiveness in adult males and females, raising the possibility that gonadal hormones play a role in mediating ethanol effects on HPA function. To address this possibility, two studies were conducted to test the hypothesis that the differential alterations in HPA activity observed in E compared to control males are mediated, at least in part, by ethanol-induced changes in HPG effects on HPA regulation. The first study compared the effects of gonadectomy (GDX) on HPA and HPG activity in adult male offspring from prenatal E, pair-fed (PF) and ad libitum-fed control (C) dams. There were no differences among groups in basal testosterone levels under intact conditions. However, E males showed increased adrenocorticotropin but blunted testosterone and luteinizing hormone (LH) responses to restraint stress compared to PF and/or C rats, and no stress-induced elevation in arginine vasopressin (AVP) mRNA levels. GDX eliminated these differences among groups. The second study explored dose-related effects of testosterone on HPA regulation. Testosterone had less of an inhibitory effect on stress-induced CORT and LH increases in E than in PF and C males. Furthermore, testosterone had a reduced effect on central corticotropin-releasing hormone pathways, but an increased effect on central AVP pathways in E compared to PF and/or C males. Importantly, reduced androgen receptor (AR) mRNA levels, possibly reflecting downregulation of AR in key brain areas, may counteract the increased inhibitory AVP signals upstream from the paraventricular nucleus, and thus contribute to the HPA hyperresponsiveness seen in E males. Together these findings suggest that central regulation of both the HPA and HPG axes are altered by prenatal ethanol exposure. The capacity of testosterone to regulate HPA activity is altered in E males, with some effects mediated by the nutritional effects of ethanol. These changes would impair the ability to maintain homeostasis in E animals and have implications for the development of secondary disabilities in children with Fetal Alcohol Spectrum Disorder.

Thesis (M.S.P.H.)--University of Michigan, 1940.