Endocrine
A number of tissues, including the brain, pituitary, immune system, placenta, mammary gland, and testis, may be self-contained units of GH regulation, production, and action. The production of GH and GH-releasing factors outside the hypothalamo-pituitary axis complements, rather than replaces, the traditional endocrine interactions between GH-releasing factors, GH, and its target tissues.
Leukemia inhibitory factor (LIF) levels are elevated in sepsis and correlate with shock and poor prognosis. We have previously shown that lipopolysaccharide (LPS) administration induces hypothalamic and pituitary LIF expression in vivo, which is associated with the acute rise in circulating adrenocorticotrophic hormone (ACTH) levels. As AtT-20 cells respond to LIF, we established murine LIF (mLIF)...
We have shown that the glucagon irresponsiveness to hypoglycemia in diabetic rats is markedly improved by correction of hyperglycemia independent of insulin. In contrast, normalization of glycemia by insulin did not improve this response. To find out whether these glucagon responses reflect changes in islet glucagon, we directly quantified glucagon area and content in each pancreatic islet by using...
The sudden appearance of prolactin-releasing cells during the early postnatal period of the rat is initiated by a small milk-borne peptide. Depriving newborn rats of this early milk factor severely retards mammotrope differentiation during the neonatal period. In the present work, we extend our study of early milk deprivation to the adult. To this end, newborn litters were crossfostered onto mothers...
Several meglitinide analogs are currently under investigation as potential insulinotropic tools for the treatment of noninsulin-dependent diabetes. The present study aimed to further insight into the effect of these agents on the secretion of insulin, glucagon, and somatostatin by the isolated perfused pancreas. Both repaglinide (0.01 μM) and A-4166 (1.0 μM) stimulated insulin and somatostatin release,...
The glucocorticoid receptor (GR) is a ligand-activated nuclear transcription factor, and AP-1 (Fos/Jun or Jun/Jun) is a transcription factor whose components are nuclear proteins encoded by c-fos and c-jun protooncogenes. Serum stimulation of serum-starved NIH 3T3 cells resulted in an approx 188-fold induction of c-fos mRNA at 30 min and an approximately ninefold induction of c-jun mRNA at 1 h, followed...
The intact rat adrenal gland in short-term (3-h) organ culture may be amenable for the identification of factors involved in regulating adrenal cell apoptosis under defined conditions. In this model, culturing in the absence of trophic support (basal; control) triggered apoptosis in the intact rat adrenal gland; oligonucleosome formation, a measure of apoptosis, was 56.4-fold greater than that of...
Streptozotocin-(STZ) treated diabetic male rats have significant reproductive endocrinopathy. To determine the functional responsiveness of luteinizing hormone-releasing hormone (LHRH) neurons in STZ-treated diabetic male rats, stimulated LHRH release was assessed using hypothalami from short-term STZ-treated, STZ-treated insulin-replaced, and control male rats. LHRH release from control, STZ-treated,...
The objectives of these experiments were (1) to determine if prostaglandin F2α (PGF2α) decreased mRNA encoding 3β-hydroxysteroid dehydrogenase/d5,Δ4 isomerase (3β-HSD) specifically in large steroidogenic luteal cells, which contain the high affinity receptors for PGF2α; and (2) to determine if the decreased concentration of mRNA encoding 3β-HSD following administration of PGF2α was associated with...
Cyclin D1 plays a key role in the regulation of the G1/S transition through the cell cycle. Deregulation of cyclin D1, most often leading to overexpression of the gene, has been reported in many tumor types. It has been suggested that cyclin D1 overexpression could be an alternative mechanism for pRb inactivation. We have previously found Rb gene mutations in 55% of malignant thyroid tumors. In the...
The interaction among parathyroid hormone (PTH), calcitonin (CT), and glucocorticoids on blood calcium (Ca) was examined. Prior studies had shown that adrenalectomy (ADX) reduced the fall in blood calcium in rats after parathyroidectomy (PTX). Convincing evidence was provided showing that the ADX effect in PTX rats was due to the loss of corticosterone, the major glucocorticoid in rats; restoring...
Our knowledge of prohormone and proneuropeptide processing and its relationship to the secretory pathway has advanced significantly in the last five years. The recent discovery of the prohormone convertase family of proteolytic enzymes has provided new candidates for the prohormone and proneuropeptide convertases. The increasing appreciation of the role of proteolysis in diverse cellular processes...
The decline in the release of various anterior pituitary hormones, particularly prolactin (PRL), as a result of exposure to inhibitory, short-day photoperiods in long-day breeders is a well-documented phenomenon. This alteration in the hypothalamic-hypophyseal-gonadal axis is largely controlled by changes in the duration of the nocturnal melatonin pulse secreted by the pineal gland. Increased duration...
The mechanism of arginine vasopressin (AVP) action in Leydig cells was investigated, and compared to the effects of phorbol-13-myristate-12-acetate (PMA) and interleukin-1β (IL-1β). Previous reports suggested that AVP inhibits Leydig cell testosterone production at the level of 17α-hydroxylase/C17-lyase activity. The present study confirms and extends these observations, and contrasts the effects...
Leptin is an important hormone that has potent effects on appetite and body weight. The regulation of leptin gene expression and secretion by corticosteroids and insulin was studied in the rat. Adrenalectomy resulted in a significant reduction in leptin gene expression and secretion. The reduction was corrected by hormonal replacement with corticosterone pellets, showing that normal levels of circulating...
ATP-sensitive K+ (K ATP) channels modulated by sulfonylurea compounds have been previously identified in the anterior pituitary of the rat and have been demonstrated to influence GH release. Recently, a sulfonylurea receptor (SUR) has been cloned from an islet cell tumor and identified as a member of the ATP binding cassette superfamily capable of coupling with inwardly rectifying potassium channels...
Insulin-like growth factor-I (IGF-I) plays an essential role in reproductive function. Leydig cells express specific IGF-I receptors, and IGF-I enhances human chorionic gonadorphin (hCG)-induced testosterone formation. In the present study, we evaluate the effect of IGF-I on the gene expression and protein levels of steroidogenic acute regulatory protein (StAR), the rate-limiting step in steroidogenesis...
We localized immunoreactive androgen receptors in the central nervous system (CNS) of fetal and adult male rhesus macaques by immunocytochemisty using an affinity-purified polyclonal antibody to the first 21 amino acids of the human androgen receptor (AR). This antibody caused a shift in the mobility of AR-bound 3H-DHT on a sucrose gradient and recognized a protein of approx 116 kDa on Western blot...