Endocrinology
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Although increased hypothalamo-pituitary-adrenocortical (HPA) activity has been reported in diabetic patients, the mechanisms underlying hyperactivation are still unclear. We investigated whether alterations in pituitary, adrenal and/or glucocorticoid negative feedback sensitivity in diabetes are responsible for 1) the impaired HPA response to stress and 2) basal hyperactivation of the HPA axis. Normal control, untreated streptozotocin-diabetic and insulin-treated diabetic rats were chronically catheterized. ⋯ Administration of CRH and ACTH revealed reduced pituitary and adrenal sensitivity in untreated diabetic animals compared with both control and insulin-treated diabetic animals. The dexamethasone suppression test indicated decreased glucocorticoid negative feedback sensitivity in diabetic rats, which was restored with insulin treatment. In conclusion, these studies demonstrate that: 1) impaired stress responsiveness of the diabetic HPA axis involves both decreased pituitary and adrenal sensitivity; and 2) basal hyperactivation of the diabetic HPA axis in the morning is due, in part, to decreased glucocorticoid negative feedback sensitivity.
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High doses of GH, used to induce anabolism in prolonged critically ill patients, unexpectedly increased mortality. To further explore underlying mechanisms, a valid animal model is needed. Such a model is presented in this study. ⋯ PRL secretion was impaired in the critically ill animals exclusively on d 8. TSH and PRL responses to GHRP-2 and TRH were increased only on d 1. In conclusion, this rabbit model of acute and prolonged critical illness reveals several of the clinical, biochemical, and endocrine manifestations of the human counterpart.
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Searching for novel genes involved in tissue remodeling during ovarian folliculogenesis, we carried out differential display RT-PCR (DDRT-PCR) on RNA from gonadotropin-stimulated rat granulosa cells (GC). GC from preantral and early antral follicles in immature rat ovaries were cultured in serum-free medium containing no hormone (control), recombinant human FSH (10 ng/ml), 5alpha-dihydrotestosterone (DHT; 10(-6) M), or FSH plus DHT. Total cellular RNA was extracted from cells at 6, 12, 24, and 48 h of treatment for DDRT-PCR analysis, corresponding to an estimated 60% saturation of the messenger RNA (mRNA) population. ⋯ In situ hybridization confirmed GC in preantral/early antral follicles as principal sites of CTGF and LO mRNA expression. We conclude that expression of CTGF and LO mRNAs is inversely related to GC differentiation. The encoded proteins probably have roles in the regulation of tissue remodeling and extracellular matrix formation during early follicular development.
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Myometrial contractions of labor result from an increase in myometrial activation and stimulation. Activation develops through the expression of contraction associated proteins (CAPs), including oxytocin receptors (OTR), connexin-43 (Cx-43), and prostaglandin F2 alpha, receptors (FP). Stimulation involves increases in contractile agonists including prostaglandin E2 (PGE2) and prostaglandin F2 alpha. (PGF2 alpha) that may result from increases in prostaglandin endoperoxide H synthase (PGHS)-2. ⋯ Uterine PGF2 alpha values were increased only at the time of term birth, but PGE2 was elevated during both preterm and term labor. These data suggest that existing levels of PGF2 alpha are sufficient for preterm birth when CAP expression is increased, but term labor requires increases in PGE2, PGF2alpha, and CAPs. The PGHS-2 messenger RNA expression pattern suggests that it is a CAP.
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Leptin is a circulating hormone that controls food intake and energy homeostasis. Little is known about leptin entry into the central nervous system (CNS). The blood-cerebrospinal fluid (CSF) barrier at the choroid plexus and the blood-brain barrier (BBB) at the cerebral endothelium are two major controlling sites for entry of circulating proteins into the brain. ⋯ In contrast, low affinity carriers for leptin (KM = 88 to 345 ng/ml) were found at the BBB in the CNS regions outside the hypothalamus (e.g. cerebral cortex, caudate nucleus, hippocampus). Our findings suggest a key role of high affinity leptin transporters in the hypothalamus and choroid plexus in regulating leptin entry into the CNS and CSF under physiological conditions. Low affinity transporters at the BBB outside the hypothalamus could potentially contribute to overall neuropharmacological effects of exogenous leptin.