Sites of action of testosterone and estradiol on longitudinal bone growth

1983 ◽  
Vol 244 (2) ◽  
pp. E135-E140 ◽  
Author(s):  
J. O. Jansson ◽  
S. Eden ◽  
O. Isaksson
Keyword(s):  
Replacement Therapy ◽  
Bone Growth ◽  
Body Weight Gain ◽  
Inhibitory Effect ◽  
Body Growth ◽  
Female Rats ◽  
Male Rats ◽  
Longitudinal Bone Growth ◽  
Sites Of Action ◽  
Different Doses

In this study the mechanisms by which sex steroids influence body growth were investigated. The effect of different doses of testosterone propionate on longitudinal bone growth and body weight gain was studied in a) gonadectomized male rats, b) gonadohypophysectomized male rats, and c) gonadohypophysectomized male rats given replacement therapy with bovine growth hormone (bGH). The effect of different doses of estradiol benzoate on the same growth parameters was studied in female rats divided into the same experimental groups as the males. Accumulated longitudinal bone growth was determined using oxytetracycline as an intravital marker. Testosterone caused a dose-dependent increase in longitudinal bone growth in gonadectomized male rats. In contrast, testosterone exerted no significant increase in longitudinal bone growth in gonadohypophysectomized male rats with and without bGH replacement therapy. Treatment with estrogen inhibited longitudinal bone growth and body weight gain. The inhibitory effect of estradiol was approximately the same in gonadohypophysectomized female rats given bGH replacement therapy as in gonadectomized female rats. The results suggest that testosterone exerts its stimulatory effect on body growth mainly by modulating hypothalamopituitary functions, e.g., by altering the secretory pattern of GH. On the other hand, it seems that changes in the hypothalamopituitary functions are less significant for the inhibitory effect of estradiol on body growth. It is concluded from this study that the sites of action for estrogen and testosterone in modulating body growth in the rat are different.

SEX DIFFERENCE IN THE INHIBITORY EFFECT OF ASPIRIN UPON THE DEVELOPMENT OF OCCLUSIVE ARTERIAL THROMBOSIS IN RATS

1987 ◽  
Author(s):  
A Uzunova
Keyword(s):  
Arterial Thrombosis ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Female Rats ◽  
Male Rats ◽  
Significant Difference ◽  
Female Wistar Rats ◽  
Dose Dependent ◽  
Prostaglandin System ◽  
Different Doses

The aim of the study was to investigate the effect of aspirin upon the development of occlusive arterial thrombosis in rats of either sex. For this purpose 3 months old male and female Wistar rats were pretreated with three different doses of aspirin: 10, 30 and 60 mg/kg b.w., orally by stomach tube, 3 hours before the thrombosis procedure. Occlusive arterial thrombosis was induced by the method of Hornstra and Vendel-mans-Starrenburg (1973). The dry thrombus weight (TW) and the obstruction time (OT) of the bypass-cannula served as criteria for the degree of the development of thrombosis.The results showed a dose-dependent statistically significant inhibition of arterial thrombosis in male rats by all doses of aspirin studied. TW was decreased 2, 2.5 and 9 times by 10, 30 and 60 mg/kg aspirin respectively. OT was significantly prolonged in male rats by all doses of aspirin studied. Inhibition of arterial thrombosis in female rats was achieved only by the largest dose of aspirin tested - 60 mg/kg: TW was decreased and OT was prolonged. Paradoxically, female rats treated with 10 mg/kg aspirin showed a tendency for augmentation of arterial thrombosis which contrasted to the significantly decreased TW and prolonged OT of male rats given 10 mg/kg aspirin. Female rats treated with 30 mg/kg aspirin showed only a tendency for inhibition of arterial thrombosis without any significant difference for both, TW and OT. The results were interpreted as suggestive the existance of sex differences in cyclooxygenase inhibition by aspirin and/or the prostaglandin system in rats. The data obtained were in agreement with epidemiological observation of uneffectiveness of aspirin treatment of female patients with stroke. They also showed the need for the most appropriate dose of aspirin for clinical purposes which might be effective in females too.

Characterization of the inhibitory roles of RFRP3, the mammalian ortholog of GnIH, in the control of gonadotropin secretion in the rat: in vivo and in vitro studies

2010 ◽  
Vol 299 (1) ◽  
pp. E39-E46 ◽  
Author(s):  
R. Pineda ◽  
D. Garcia-Galiano ◽  
M. A. Sanchez-Garrido ◽  
M. Romero ◽  
F. Ruiz-Pino ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Gonadotropin Secretion ◽  
Male And Female Rats ◽  
Sites Of Action ◽  
Lh Secretion

RF-amide related peptides (RFRP), as putative mammalian orthologs of the avian gonadotropin-inhibitory hormone (GnIH), have been proposed as key regulators of gonadotropin secretion in higher vertebrates. Yet considerable debate has arisen recently on their physiological relevance and potential mechanisms and sites of action. Present studies were undertaken to further characterize the effects of RFRP on LH and FSH secretion by a combination of in vivo and in vitro approaches in male and female rats. Initial screening via intracerebroventricular (icv) administration of different analogs of RFRP1 (RFRP1–12 and RFRP1–20) and RFRP3 (RFRP3–8 and RFRP3–17), as well as the related neuropeptide FF (NPFF8), to gonadectomized (GNX) female rats evidenced significant, albeit modest, inhibitory effects on LH secretion only for RFRP3–8 and RFRP3–17, which were detectable at the high dose rage (1 nmol for RFRP3–8, 5 nmol for RFRP3–17). This moderate inhibitory action was also documented after icv administration of RFRP3–8 to intact and GNX male rats. In addition, systemic (intravenous) administration of RFRP3–8 decreased the circulating levels of both gonadotropins in GNX male rats. Likewise, RFRP3–8 inhibited basal and GnRH-stimulated LH secretion by pituitaries from GNX males in vitro. This inhibitory effect was blocked by the antagonist of RFRP receptors, RF9. In summary, our results support a putative inhibitory role of RFRP3 as ortholog of GnIH in the regulation of gonadotropin secretion in mammals, which appears to involve direct pituitary actions as well as potential central (hypothalamic) effects.

Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats

2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Rat Kidney ◽  
Late Pregnancy ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Renal Vasoconstriction ◽  
Dependent Inhibition

20-Hydroxyeicosatetraenoic acid (20-HETE), which promotes renal vasoconstriction, is formed in the rat kidney primarily by cytochrome P-450 (CYP) 4A isoforms (4A1, 4A2, 4A3, 4A8). Nitric oxide (NO) has been shown to bind to the heme moiety of the CYP4A2 protein and to inhibit 20-HETE synthesis in renal arterioles of male rats. However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats. Incubation of recombinant CYP4A1 and 4A3 proteins with sodium nitroprusside (SNP) shifted the absorbance at 440 nm, indicating the formation of a ferric-nitrosyl-CYP4A complex. The absorbance for CYP4A3 was about twofold higher than that of CYP4A1. Incubation of SNP or peroxynitrite (PN; 0.01–1 mM) with CYP4A recombinant membranes caused a concentration-dependent inhibition of 20-HETE synthesis, with both chemicals having a greater inhibitory effect on CYP4A3-catalyzed activity. Moreover, incubation of CYP4A1 and 4A3 proteins with PN (1 mM) resulted in nitration of tyrosine residues in both proteins. In addition, PN and SNP inhibited 20-HETE synthesis in renal microvessels from female rats by 65 and 59%, respectively. We previously showed that microvessel CYP4A1/CYP4A3 expression and 20-HETE synthesis are decreased in late pregnancy. Therefore, we investigated whether such a decrease is dependent on NO, the synthesis of which has been shown to increase in late pregnancy. Administration of NG-nitro-l-arginine methyl ester (l-NAME) to pregnant rats for 6 days ( days 15- 20 of pregnancy) caused a significant increase in systolic blood pressure, which was prevented by concurrent treatment with the CYP4A inhibitor 1-aminobenzotriazole (ABT). Urinary NO2/NO3 excretion decreased by 40 and 52% in l-NAME- and l-NAME + ABT-treated groups, respectively. Interestingly, renal microvessel 20-HETE synthesis showed a marked increase following l-NAME treatment, and this increase was diminished with coadministration of ABT. These results demonstrate that NO interacts with CYP4A proteins in a distinct manner and it interferes with renal microvessel 20-HETE synthesis, which may play an important role in the regulation of blood pressure and renal function during pregnancy.

Toxicity Assessment of 4-Amino-2-Nitrotoluene

2013 ◽  
Vol 32 (2) ◽  
pp. 113-122 ◽  
Author(s):  
John T. Houpt ◽  
Glenn J. Leach ◽  
Larry R. Williams ◽  
Mark S. Johnson ◽  
Gunda Reddy
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
Toxicity Data ◽  
Adverse Effect Level ◽  
Effect Level

4-Amino-2-nitrotoluene (4A2NT; CAS 119-32-4) is a degradation product of 2,4-dinitrotoluene. The toxicity data on 4A2NT are limited. Therefore, we collected toxicity data from rats to assess environmental and human health effects from exposures. The approximate lethal dose for both sexes was 5000 mg/kg. A 14-day toxicity study in rats was conducted with 4A2NT in the feed at concentrations of 0, 125, 250, 500, 1000, and 2000 ppm. Based on a 14-day oral dose range toxicity study with 4A2NT in the feed, 2000 ppm was selected as highest concentration for a subsequent 90-day study. An oral 90-day subchronic toxicity study in rats was conducted with concentrations of 0, 500, 1000, or 2000 ppm of 4A2NT in the feed. The calculated consumed doses of 4A2NT in the feed were 0, 27, 52, or 115 mg/kg/d for males and 0, 32, 65, or 138 mg/kg/d for females. A no-observed adverse effect level could not be determined. The lowest observed adverse effect level was 27 mg/kg/d for males and 32 mg/kg/d for female rats based upon decreased body weight gain. The decreased body weight gain in male rats was the most sensitive adverse event observed in this study and was used to derive a benchmark dose (BMD). A BMD of 23.1 mg/kg/d and BMD with 10% effect level of 15.5 mg/kg/d were calculated for male rats, which were used to derive an oral reference dose (RfD). The human RfD of 1.26 μg/kg/d was derived using current United States Environmental Protection Agency guidelines.

scholarly journals Effect of radioactive iodine-induced hypothyroidism on longitudinal bone growth during puberty in immature female rats

2018 ◽  
Vol 67 (4) ◽  
pp. 395-401 ◽  
Author(s):  
Hyeonhae Choi ◽  
Ki-Young Ryu ◽  
Jaesook Roh ◽  
Jaeman Bae
Keyword(s):  
Bone Growth ◽  
Radioactive Iodine ◽  
Female Rats ◽  
Immature Female ◽  
Longitudinal Bone Growth

scholarly journals Estradiol Stimulates Apolipoprotein A-IV Gene Expression in the Nucleus of the Solitary Tract Through Estrogen Receptor-α

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 3882-3890 ◽  
Author(s):  
Ling Shen ◽  
Yin Liu ◽  
David Q.H. Wang ◽  
Patrick Tso ◽  
Stephen C. Woods ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Nucleus Tractus Solitarius ◽  
Body Weight Gain ◽  
Gene Promoter ◽  
Estrogen Receptor Α ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Upstream Region ◽  
Apolipoprotein A

Abstract Although estrogens have been implicated in the regulation of apolipoprotein A-IV (apo A-IV) gene expression in the nucleus tractus solitarius, previous studies have not defined the molecular mechanism. The aim of this study was to examine the transcriptional mechanisms involved in regulation of apo A-IV gene expression. Using cultured primary neuronal cells from rat embryonic brainstems, we found that treatment with 10nM 17β-estradiol-3-benzoate (E2) or 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (an estrogen receptor [ER]α agonist), but not 2,3-bis(4-hydroxyphenyl)-propionitrile (an ERβ agonist), significantly increased apo A-IV gene expression, compared with vehicle treatment. This effect of E2 was abolished when the cells were incubated with E2 linked to BSA, which prevents E2 from entering cells, implying that a nongenomic mechanism of E2 is not involved. Two putative estrogen response elements were identified at the 5′-upstream region of the apo A-IV gene promoter, but only 1 of them was able to recruit ERα, leading to increased apo A-IV gene expression, as determined by chromatin immunoprecipitation assay and luciferase activity analysis. A cyclic regimen of E2 or 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol treatment for 8 cycles (4 d/cycle, mimicking the ovarian cycle of female rats) in ovariectomized female rats significantly reduced food intake and body weight gain and increased apo A-IV gene expression in the nucleus tractus solitarius, relative to vehicle. These data collectively demonstrate that nuclear ERα is the primary mediator of E2's action on apo A-IV gene expression and suggest that increased signaling of endogenous apo A-IV may at least partially mediate E2-induced inhibitory effect on feeding.

scholarly journals Amomum villosum induces longitudinal bone growth in adolescent female rats

2012 ◽  
Vol 32 (3) ◽  
pp. 453-458 ◽  
Author(s):  
Sun Haeng Lee ◽  
Ji Young Kim ◽  
Hocheol Kim ◽  
Seul Ki Park ◽  
Cho Young Kim ◽  
...  
Keyword(s):  
Bone Growth ◽  
Female Rats ◽  
Adolescent Female ◽  
Longitudinal Bone Growth ◽  
Amomum Villosum

Effect of New Calcium Supplementary Food Containing Fermented Product of Bacillus on the Longitudinal Bone Growth in the Adolescent Male Rats

2008 ◽  
Vol 37 (12) ◽  
pp. 1576-1582
Author(s):  
Jae-Yeon Lee ◽  
Young-Shik Park ◽  
Young-Hoon Kim ◽  
Kyung-Hwan Oh ◽  
Kyo-Yeol Hwang ◽  
...  
Keyword(s):  
Bone Growth ◽  
Male Rats ◽  
Adolescent Male ◽  
Supplementary Food ◽  
Longitudinal Bone Growth ◽  
Fermented Product

Circumstantial evidence for a role of the secretory pattern of growth hormone in control of body growth

1982 ◽  
Vol 99 (1) ◽  
pp. 24-30 ◽  
Author(s):  
John-Olov Jansson ◽  
Kerstin Albertsson-Wikland ◽  
Staffan Edén ◽  
Karl-Göran Thorngren ◽  
Olle Isaksson
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Replacement Therapy ◽  
Bone Growth ◽  
Injection Period ◽  
Longitudinal Bone Growth ◽  
Long Period ◽  
Hypophysectomized Rats ◽  
Secretory Pattern

Abstract. The effect of frequency of growth hormone (GH) administration on longitudinal bone growth and body weight was studied in hypophysectomized rats which were given replacement therapy with corticosteroids, thyroxine and GH with start of therapy on the day of surgery. Longitudinal bone growth, as determined by the tetracycline method, was measured during the last 5 days of the 9 day long period with replacement therapy. The daily replacement dose of GH (bGH-17:NIH) was 200 μg and was given on 1, 2, 4 or 8 occasions. Longitudinal bone growth was enhanced in the groups of animals receiving the hormone on two or more occasions per day. The most pronounced response was seen with an administration frequency of four times per day. Changes in body weight during the injection period showed similar changes. The results of the present study show that the administration frequency of growth hormone is important for the growth rate in hypophysectomized rats which have been given replacement therapy. The findings suggest that the secretory pattern of GH is an important factor for optimum growth.

scholarly journals The effect of lucerne-protein concentrate in the diet on growth, reproduction and body composition of Rats

1974 ◽  
Vol 31 (2) ◽  
pp. 147-157 ◽  
Author(s):  
E. L. Hove ◽  
Evelyn Lohrey ◽  
M. K. Urs ◽  
R. M. Allison
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Female Rats ◽  
Male Rats ◽  
Initial Growth ◽  
Protein Concentrate ◽  
Body Protein ◽  
Complete Control ◽  
Male And Female Rats ◽  
Freeze Dried

1. Protein concentrates were prepared from freshly cut lucerne by the Pirie process and freeze-dried. When supplemented with methionine or cystine and given to rats as the sole source of protein at 120 g protein/kg diet, the adjusted mean protein efficiency ratio was 2.89 (casein standard at 2.50). As a supplement to protein from barley meal the lucerne leaf-protein concentrate (LPC) was similar to casein.2. To investigate nutritional safety, lucerne LPC supplemented with methionine was given to rats at high levels for 6 months; exposure of these rats to diffuse daylight was avoided to prevent a severe disfiguring photosensitivity reaction. At a dietary protein concentration of 100 g/kg, rats grew equally well with lucerne LPC or casein. When the supplement was given at protein concentrations of 200 or 300 g/kg the rates of body-weight gain of male and female rats were less than those of control rats given casein. However, after 5 months on the diets, body-weights of male rats had nearly reached those of the controls.3. Apparent protein digestibility ratio was about 0.80 with all three levels of lucerne LPC.4. Reproduction was normal in seventeen of the eighteen female rats given the lucerne LPC at the three levels; lactation was also normal and litters were successfully raised to weaning.5. Organ weights, liver histology and blood haemoglobin were normal in male rats given the lucerne LPC for 6 months.6. Total body lipid of male rats given lucerne LPC was about half that of the control rats given casein. Body protein was slightly increased, and moisture content was higher in rats given lucerne LPC.7. The ‘whey’ remaining after precipitation of the protein from lucerne juice strongly inhibited the initial growth of mice given a complete control diet. The mice soon accommodated to the depressive effect of ‘whey’, and body-weight gains were normal during the 3rd week.

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