Resolving the growth-promoting and metabolic effects of growth hormone: Differential regulation of GH-IGF-I system components

Growth hormone regulates numerous processes in vertebrates including growth promotion and lipid mobilization. During periods of food deprivation, growth is arrested yet lipid depletion is promoted. In this study, we used rainbow trout on different nutritional regimens to examine the regulation of growth hormone (GH)-insulin-like growth factor-I (IGF-I) system elements in order to resolve the growth-promoting and lipid catabolic actions of GH. Fish fasted for 2 or 6 weeks displayed significantly reduced growth compared to their fed counterparts despite elevated plasma GH, while refeeding for 2 weeks following 4 weeks of fasting partially restored growth and lowered plasma GH. Fish fasted for 6 weeks also exhausted their mesenteric adipose tissue reserves. Sensitivity to GH in the liver was reduced in fasting fish as evidenced by reduced expression of GH receptor type 1 (GHR 1) and GHR 2 mRNAs and by reduced (125)I-GH binding capacity. Expression of GHR 1 and GHR 2 mRNAs also was reduced in the gill of fasted fish. In adipose tissue, however, sensitivity to GH, as indicated by GHR 1 expression and by (125)I-GH binding capacity, increased after 6 weeks of fasting in concert with the observed lipid depletion. Fasting-associated growth retardation was accompanied by reduced expression of total IGF-I mRNA in the liver, adipose and gill, and by reduced plasma levels of IGF-I. Sensitivity to IGF-I was reduced in the gill of fasted fish as indicated by reduced expression of type 1 IGF-I receptor (IGFR 1A and IGFR 1B) mRNAs. By contrast, fasting did not affect expression of IGFR 1 mRNAs or (125)I-IGF-I binding in skeletal muscle and increased expression of IGFR 1 mRNAs and (125)I-IGF-I binding in cardiac muscle. These results indicate that nutritional state differentially regulates GH-IGF-I system components in a tissue-specific manner and that such alterations disable the growth-promoting actions of GH and promote the lipid-mobilizing actions of the hormone.     

Oxytocin stimulates cerebral blood flow in rainbow trout (Oncorhynchus mykiss) through a nitric oxide dependent mechanism

Our knowledge of the regulation of cerebral blood flow (CBF) in ectothermic vertebrates is still very limited. In endothermic vertebrates several peptides have been shown to affect CBF through nitric oxide (NO) dependent mechanisms. Using epi-illumination microscopy in rainbow trout in vivo, we have examined the effects of topically administered oxytocin, arginine vasopressin, substance P and bradykinin on the CBF (measured as erythrocyte velocity in venules on the optic lobes). Of these peptides, only oxytocin induced a dose dependent increase in CBF velocity. Blood pressure remained unchanged and the effect was suppressed by the NOS inhibitor, N(omega)-nitro-L-arginine. This indicates that oxytocin causes NO mediated vasodilation in rainbow trout brain.     

Metastatic bronchogenic carcinoma masquerading as a felon

This report describes a rare occurrence of a subcutaneous metastatic bronchogenic carcinoma to the distal fingertip. The original clinical presentation suggested an infectious process. Subsequent roentgenograms, sterile cultures, and positive biopsy material revealed that the lesion started as a subcutaneous metastasis that secondarily involved adjacent bone. Amputation of the digit was performed.     

Study of function and maturation of monocytes in morbidly obese individuals

In recent years there has been an intense interest in understanding the mechanisms involved in immune modulation associated with dietary restriction. In this study we have investigated maturation of peripheral blood monocytes in morbidly obese patients using an in vitro culture system. At the end of the culture, the matured monocytes (macrophages) were quantitated. Though there was no detectable functional defect observed in the matured monocytes in vitro, there was a quantitative difference in maturation among the monocytes plated. The number of monocytes that matured into macrophages in obese patients was 3.29 ± 2.41 × 10⁴ cells per milliliter of blood, as compared to 8.24 ± 3.14 × 10⁴ per milliliter of blood in normal volunteers. This difference was found to be statistically significant at P < 0.001. These results indicate a possible development of an intrinsic defect among morbidly obese individuals.     

In vitro androgenicity in pulp and paper mill effluents

Pulp and paper mill effluents were examined for in vitro androgenicity using a recombinant yeast-based androgen receptor assay. Low levels of androgenic effects were detected in extracts of some effluents after activated sludge treatment. Yeast cell growth cell was inhibited in some samples, and this interfered with the androgenic response. Solid-phase fractionation revealed androgenicity after partial separation of components in the effluents. Comparison of levels in untreated effluent and in effluent treated in an aerated lagoon showed that this treatment had only a marginal effect on androgenicity. An assay of the fractions eluted with increasing concentrations of methanol showed that androgenic compounds were low to moderately lipophilic. In an attempt to identify these compounds, a number of wood-related compounds (guaiacol, vanillin, beta-sitosterol, betulin, pinosylvin-O-methyl ether, and a wood extract enriched in lignans) were examined but were found not to be androgenic. Raw process water was not androgenic, but water from a highly humified lake and process water from the production of pulp from partly decayed wood had low androgenicity. It therefore can be plausibly suggested that the androgens originated in decaying wood. An assay of androgenicity in the bile of juvenile rainbow trout exposed to effluents for 3 weeks showed increased dose-dependent levels of androgens after enzymatic hydrolysis of hormone conjugates.