Metabolic Changes Associated With Transplantable Acth-Producing Pituitary Tumors of the Mouse

Abstract

Following the implantation of adrenocorticotrophin-producing tumors into LAF1 mice, a reproducible syndrome was observed which was characterized by adrenal cortical hypertrophy, thymic atrophy, lymphopenia, ovarian atrophy, cessation of estrus cycles, obesity, polydipsia, and polyuria. These changes appeared after intervals of a few weeks or several months, depending on the secretory activity of the tumor. Metabolic balance studies indicated an increased excretion of nitrogen and potassium. In place of an intolerance to glucose in the tumor-bearing mice, there was an apparently increased tolerance, presumably due to the presence of the large tumor mass. Observations on intact, castrated, and hypophysectomized mice bearing ACTH tumors suggested that the C21 steroids of LAF1 mice possess moderate glucocorticoid as well as discernible mineralocorticoid activity; the C19 steroids apparently are either very weak or inactive androgens, but may be capable of directly affecting the anterior pituitary and the vagina.

An N-Ethyl-N-Nitrosourea Induced Corticotropin-Releasing Hormone Promoter Mutation Provides a Mouse Model for Endogenous Glucocorticoid Excess

“…Of note, the Crh − 120 /+ mice were not hyperpigmented (examined on a C3H/HeH genetic background), despite the presence of increased pituitary Pomc expression ( Figure 2 F). The absence of hyperpigmentation is in keeping with other reported ACTH-driven Cushing's mouse models such as mice transplanted with ACTH-producing pituitary tumors ( 33 ) or in the polyoma large T antigen transgenic mice that develop ACTH-producing tumors ( 34 , 35 ). We postulate that although Pomc expression was elevated in CS mice, the synthesized POMC peptide may not have undergone complete posttranslational processing to produce peptides that promote pigmentation, such as α-MSH.…”

Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation

“…Mono-culture models of ACTHsecreting AtT20 pituitary cells [45][46][47][48][49] and corticosterone-secreting Y-1 adrenal cells [50][51][52][53][54] derived from mice were developed to verify whether these cells secrete hormones only upon stimulation by exposure to cold. AtT-20 was originally induced in a mouse that received ionizing radiation [55] and has been maintained in LAF-1 mice of both sexes (MS) by Dr.Jacob Furth and colleagues [56] since 1957. LAF-1 mice of both sexes (4 to 6 weeks old) were purchased from Jackson laboratory (Bar Harbor, ME, USA).…”