Direct effects of medroxyprogesterone acetate (MPA) and megestrol acetate (MGA) on rat testicular steroidogenesis

1980 ◽  
Vol 94 (3) ◽  
pp. 419-425 ◽  
Author(s):  
Robert L. Barbieri ◽  
Kenneth J. Ryan

Abstract. The effects of MPA and MGA on rat testicular steroidogenesis were examined by studying: 1) serum testosterone in hCG primed animals treated with MPA or MGA, 2) testosterone synthesis in rat Leydig cells cultured with MPA or MGA, 3) MPA and MGA binding to rat testis microsomal cytochrome P-450 and 4) MPA and MGA inhibition of enzymes of rat testicular steroidogenesis. In immature rats receiving 1.0 IU of hCG per day 20 mg/kg of MPA or MGA reduced serum testosterone by 57 and 56%, respectively. In mature male rats receiving 50.0 IU of hCG per day 20 mg/kg of MPA or MGA reduced serum testosterone by 40 and 29%, respectively. In rat interstitial cells cultured with 10 ng of rat LH, 1 μm MPA or MGA inhibited testosterone production by 32 and 23%, respectively. Addition of MPA or MGA to microsomal preparations resulted in a type I cytochrome P-450 difference spectrum. MPA and MGA inhibited rat testicular 17α-hydroxylase, 17,20-lyase, and the 3β- and 17β-hydroxysteroid dehydrogenases. These findings suggest that MPA and MGA inhibit rat testicular steroidogenesis in vivo and in vitro.

1975 ◽  
Vol 53 (5) ◽  
pp. 873-879 ◽  
Author(s):  
Jacob V. Aranda ◽  
Kenneth W. Renton

The effect of glucagon on the components of the hepatic microsomal electron transport chain (NADPH oxidase, NADPH cytochrome c reductase (EC 1.6.2.4), cytochrome P-450, and NADPH cytochrome P-450 reductase), and on two representative oxidative pathways (aminopyrine N-demethylation, a type I substrate oxidation; and aniline p-hydroxylation, a type II substrate oxidation) was determined. Microsomes from rats pretreated with glucagon (300 μg/kg per day for 3 days) showed a significant decrease in NADPH oxidation and in aminopyrine N-demethylation with a prolonged hexobarbital sleeping time, and a significant increase in aniline p-hydroxylation. Microsomes from rats pretreated with a lower dose of glucagon (30 μg/kg per day for 3 days) showed a significant decrease in the microsomal N-demethylation of aminopyrine. Glucagon had no effect when added in vitro to microsomes, suggesting that the in vivo effects of glucagon are mediated indirectly in the intact animal.


1987 ◽  
Vol 116 (1) ◽  
pp. 138-144 ◽  
Author(s):  
Dorothy I. Shulman ◽  
Margaret Sweetland ◽  
Gregory Duckett ◽  
Allen W. Root

Abstract. The GH secretory response to varying doses (15, 30, 60 μg/kg) of sc administered hGHRH 1–44 (or normal saline) was measured in vivo in 10, 20, 30, 40, 50, 60 and 130 days old pentobarbital-anaesthetized, male rats. The 10-min GH level and ΔGH were in general significantly greater in older rats (50, 60, 130 days old) than in younger rats (10, 20 days old) following all doses hGHRH. Ten-day-old animals had no significant GH response to any dose of hGHRH tested. ΔGH correlated significantly with age (r = 0.36; P < 0.0001) and Sm-C level (r = 0.29; P < 0.01) but not with serum testosterone concentrations. Monolayer pituitary cell cultures were established in rats aged 10 to 130 days and were incubated with varying concentrations of hGHRH 1–44 (0.05, 0.5, 5.0, 50 nmol/l or incubation medium). Cultures from 10- and 20-day-old animals had a greater percentage increase over basal GH secretion than other groups at all concentrations of hGHRH tested (P < 0.05). Age-related differences in the GH secretory response to hGHRH are present in male rats from 10 to 130 days. The in vitro results reported here suggest that the increase in magnitude and sensitivity of the GH response to hGHRH observed in pubertal animals in vivo under pentobarbital anaesthesia is likely due to influences above the level of the somatotrope receptor.


2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Maria Nurminskaya ◽  
Derek Banyard ◽  
Dmitry Nurminsky ◽  
Mikhail Konoplyannikov ◽  
Kelly Beazley

Medial arterial calcification contributes to the development of isolated systolic hypertension, the most frequent type of blood pressure elevation in the elderly; complicates a variety of prevalent disorders such as diabetes and renal disease; and can develop in response to warfarin - the staple in anticoagulant therapy to millions of people. Our in vitro studies have shown that the bioflavonoid quercetin effectively prevents warfarin-induced vascular calcification in VSMCs and identified b-catenin signaling as a specific target of this effect. Here, we have tested in vivo the association of b-catenin signaling with warfarin-induced calcification and the efficacy of quercetin in preventing warfarin-induced aortic calcium accrual. Vitamin K-warfarin treatment was used for 4 weeks to induce arterial calcification in male rats. Molecular analysis demonstrates activation of b-catenin signaling in the calcified areas and osteoblast-like transformation in vascular cells. Dietary quercetin (10 mg/kg body weight) (Quercegen Pharma, Newton, MA) efficiently prevents warfarin-induced calcification (3.04+/-0.45 ug Ca in vitamin K-warfarin animals vs 0.77+/-0.08 ug Ca in quercetin supplementation per mg dry arterial tissue (n=5; p<0.05). In parallel, quercetin inhibits b-catenin signaling and phenotypic transformation in vascular smooth muscle analyzed by expression of transcription factor Runx2, collagen type I and osteocalcin. Further, quercetin diet enhances expression of VSMC markers smooth muscle actin, myosin heavy chain, sm22a and calponin, suggesting a stabilized smooth muscle phenotype of these cells. No toxic or systemic effects of quercetin treatment were observed, identifying this bioflavonoid as a putative therapeutic for vascular calcification.


1979 ◽  
Vol 82 (1) ◽  
pp. 95-104 ◽  
Author(s):  
LIISA SELIN ◽  
W. H. MOGER

SUMMARY Administration of FSH to hypophysectomized male rats has been shown to increase the capacity of the testes to secrete testosterone in response to LH. Studies were done to assess the effect of increased endogenous FSH on the response of the testis to LH. At 17 and 24 days of age, animals hemiorchidectomized at 10 days of age had significantly higher serum FSH levels and testicular weights than sham-operated rats. To study the testicular response to LH in vivo, hemiorchidectomized animals were sham-operated and the sham-operated animals were hemiorchidectomized at 17 or 24 days of age. Luteinizing hormone (30 μg/100 g body wt) or saline was administered immediately after the operation and the animals were autopsied 90 min later. Chronic hemiorchidectomy significantly increased the serum testosterone response to LH at 17 but not at 24 days of age. The testicular response to LH in vitro was also investigated. Testes from rats hemiorchidectomized or sham-operated at 10 days of age and killed at 17 and 24 days of age were incubated for 3 h in the presence or absence of 100 ng LH/ml incubation medium. Significantly more 5α-androstane-3α,17β-diol and androsterone were produced by the testes from hemiorchidectomized than from sham-operated animals at 17 days of age but not at 24 days of age. The production of testosterone in vitro was not influenced by hemiorchidectomy at either age. These results suggest that serum FSH concentration is the factor limiting LH responsiveness before but not after the prepubertal increase in FSH levels. However, treatment of intact rats from 10 to 16 days of age with 20 μg rat FSH/day did not increase the serum testosterone response to LH.


2020 ◽  
pp. 40-50
Author(s):  
A. Nikitina

Analysis of literature data presented in search engines — Elibrary, PubMed, Cochrane — concerning the risk of developing type I allergic reactions in patients with blood diseases is presented. It is shown that the most common cause of type I allergic reactions is drugs included in the treatment regimens of this category of patients. The article presents statistics on the increase in the number of drug allergies leading to cases of anaphylactic shock in patients with blood diseases. Modern methods for the diagnosis of type I allergic reactions in vivo and in vitro are considered.


2021 ◽  
Vol 8 (3) ◽  
pp. 39
Author(s):  
Britani N. Blackstone ◽  
Summer C. Gallentine ◽  
Heather M. Powell

Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes. D-banding was most often observed in electrospun collagen formed using collagen type I isolated from calfskin, often isolated within the laboratory, with short solution solubilization times. All physical and chemical methods of crosslinking utilized imparted resistance to degradation and increased strength. Cytotoxicity was observed at high concentrations of crosslinking agents and when abbreviated rinsing protocols were utilized. Collagen and collagen-based scaffolds were capable of forming engineered tissues in vitro and in vivo with high similarity to the native structures.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Peng Gao ◽  
Xianwei Ma ◽  
Ming Yuan ◽  
Yulan Yi ◽  
Guoke Liu ◽  
...  

AbstractUbiquitination is one of the most prevalent protein posttranslational modifications. Here, we show that E3 ligase Nedd4l positively regulates antiviral immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3. Deficiency of Nedd4l significantly impairs type I interferon and proinflammatory cytokine production induced by virus infection both in vitro and in vivo. Nedd4l deficiency inhibits virus-induced ubiquitination of TRAF3, the binding between TRAF3 and TBK1, and subsequent phosphorylation of TBK1 and IRF3. Nedd4l directly interacts with TRAF3 and catalyzes K29-linked ubiquitination of Cys56 and Cys124, two cysteines that constitute zinc fingers, resulting in enhanced association between TRAF3 and E3 ligases, cIAP1/2 and HECTD3, and also increased K48/K63-linked ubiquitination of TRAF3. Mutation of Cys56 and Cys124 diminishes Nedd4l-catalyzed K29-linked ubiquitination, but enhances association between TRAF3 and the E3 ligases, supporting Nedd4l promotes type I interferon production in response to virus by catalyzing ubiquitination of the cysteines in TRAF3.


2021 ◽  
Vol 19 ◽  
pp. 228080002198969
Author(s):  
Min-Xia Zhang ◽  
Wan-Yi Zhao ◽  
Qing-Qing Fang ◽  
Xiao-Feng Wang ◽  
Chun-Ye Chen ◽  
...  

The present study was designed to fabricate a new chitosan-collagen sponge (CCS) for potential wound dressing applications. CCS was fabricated by a 3.0% chitosan mixture with a 1.0% type I collagen (7:3(w/w)) through freeze-drying. Then the dressing was prepared to evaluate its properties through a series of tests. The new-made dressing demonstrated its safety toward NIH3T3 cells. Furthermore, the CCS showed the significant surround inhibition zone than empty controls inoculated by E. coli and S. aureus. Moreover, the moisture rates of CCS were increased more rapidly than the collagen and blank sponge groups. The results revealed that the CCS had the characteristics of nontoxicity, biocompatibility, good antibacterial activity, and water retention. We used a full-thickness excisional wound healing model to evaluate the in vivo efficacy of the new dressing. The results showed remarkable healing at 14th day post-operation compared with injuries treated with collagen only as a negative control in addition to chitosan only. Our results suggest that the chitosan-collagen wound dressing were identified as a new promising candidate for further wound application.


2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.


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