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1.
Oncogene ; 35(17): 2197-207, 2016 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-26257057

RESUMO

Enhanced sensitivity to Wnts is an emerging hallmark of a subset of cancers, defined in part by mutations regulating the abundance of their receptors. Whether these mutations identify a clinical opportunity is an important question. Inhibition of Wnt secretion by blocking an essential post-translational modification, palmitoleation, provides a useful therapeutic intervention. We developed a novel potent, orally available PORCN inhibitor, ETC-1922159 (henceforth called ETC-159) that blocks the secretion and activity of all Wnts. ETC-159 is remarkably effective in treating RSPO-translocation bearing colorectal cancer (CRC) patient-derived xenografts. This is the first example of effective targeted therapy for this subset of CRC. Consistent with a central role of Wnt signaling in regulation of gene expression, inhibition of PORCN in RSPO3-translocated cancers causes a marked remodeling of the transcriptome, with loss of cell cycle, stem cell and proliferation genes, and an increase in differentiation markers. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Proteínas de Membrana/genética , Proteínas Wnt/genética , Aciltransferases , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Membrana/antagonistas & inibidores , Camundongos , Processamento de Proteína Pós-Traducional , Células-Tronco/efeitos dos fármacos , Proteínas Wnt/antagonistas & inibidores , Via de Sinalização Wnt/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Biol Reprod ; 66(4): 877-85, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11906904

RESUMO

Transgenic mice carrying rat androgen-binding protein (ABP) genomic DNA express high amounts of testicular ABP and develop a progressive impairment of spermatogenesis. To understand the mechanism of these changes, we have studied the pattern of testicular germ cell proliferation from 7 to 360 days of age in wild-type (WT) control and transgenic homozygous (ABP-TG) mice by flow cytometry after labeling DNA in isolated germ cells with propidium iodide. At all ages studied, the body weight of the ABP-TG mice was lower than that of age-matched WT controls. Significantly reduced testicular weight and total germ cell number in the ABP-TG mice were evident from Day 30 and Day 60, respectively. Flow cytometric analysis of isolated germ cells revealed that the number of germ cells undergoing proliferation (S-phase cells) was identical in WT control and ABP-TG mice up to Day 14. Subsequently, the number of germ cells in S-phase was consistently higher in ABP-TG than in WT mice. The number of primary spermatocytes was significantly increased starting from Day 60, and the numbers of round and elongated spermatids were significantly reduced in the ABP-TG animals from Day 21 and Day 60 onwards, respectively. Immunocytometry for intracellular ABP at 90 days of age revealed that the percentage of ABP-containing germ cells was greater in ABP-TG than in WT mice. The continuous presence of ABP in mouse seminiferous tubules at greater than physiological concentrations facilitates the formation of primary spermatocytes but impairs subsequent transformation to round and elongated spermatids. Based on our observations and the analysis of the available literature, the most likely mechanism for production of these effects is sustained reduction in the bioavailability of androgens.


Assuntos
Proteína de Ligação a Androgênios/genética , Divisão Celular , Expressão Gênica , Espermatozoides/citologia , Testículo/citologia , Envelhecimento , Proteína de Ligação a Androgênios/análise , Androgênios/fisiologia , Animais , DNA/biossíntese , Citometria de Fluxo , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Tamanho do Órgão , Ratos , Fase S , Túbulos Seminíferos/química , Contagem de Espermatozoides , Espermátides/citologia , Espermatogênese , Espermatogônias/citologia , Espermatogônias/metabolismo , Espermatozoides/química , Testículo/química , Testículo/metabolismo
3.
Endocr Res ; 27(1-2): 223-32, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11428714

RESUMO

The impact of progesterone on serum hormonal profiles in the presence and absence of gonads was studied in adult male and female albino rats. Progesterone was administered intramuscularly for 30 days at a dose of 1 mg/100g body weight/day. Serum testosterone, estradiol and prolactin titres decreased in male and female rats with intact gonads given progesterone. While the levels of both luteinizing hormone (LH) and follicle stimulating hormone (FSH) decreased in male rats with intact gonads, only FSH decreased in female rats. The inhibitory effect of progesterone on serum estradiol, LH, FSH and prolactin persisted even after gonadectomy in male rats. This persistent inhibitory effect of progesterone was also seen on serum testosterone, FSH and prolactin levels of female rats. Ovariectomy modified progesterone action on LH, as is evident from the decreased levels of LH observed only in ovariectomized rats given progesterone. While progesterone had no effect on serum T3 and T4 in male rats, gonadectomy altered the levels of T3 and T4 in male and female rats. Progesterone increased the levels of T3 and decreased the levels of T4 in ovariectomized rats. Growth hormone (GH) and thyroid stimulating hormone (TSH) levels seem to be resistant to changes in progesterone titre, irrespective of the sex and gonadal status. The present data suggest the existence of a sex specific effect of progesterone on gonadotrophins. The data on T3, T4 and TSH reveals that progesterone has no effect on the pituitary thyroid axis in the presence of gonads.


Assuntos
Hormônios/sangue , Progesterona/farmacologia , Animais , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Masculino , Orquiectomia , Ovariectomia , Progesterona/administração & dosagem , Prolactina/sangue , Ratos , Caracteres Sexuais , Testosterona/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
4.
J Biosci ; 26(4 Suppl): 391-405, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11779954

RESUMO

Approximately 48.2% of couples of 15 to 49 years of age practice family planning methods in India. Female sterilization accounts for 34.2%, with male sterilization declining from 3.4% in 1992-93 to 1.9% in 1998-99. Use of the condom increased to 3.1% from 2.4%. There is an urgent need for research to develop new contraceptive modalities especially for men and also for women and to make existing methods more safe, affordable and acceptable. Current efforts in India to develop a male contraceptive are mainly directed towards (i) development of antispermatogenic agents to suppress sperm production, (ii) prevention of sperm maturation, (iii) prevention of sperm transport through vas deferens or rendering these sperm infertile and (iv) prevention of sperm deposition. Research work in the field of prevention of sperm transport through vas deferens has made significant advances. Styrene maleic anhydride (SMA) disturbed the electrical charge of spermatozoa leading to acrosome rupture and consequent loss in fertilizing ability of sperm. A multicentre phase-III clinical trial using SMA is continuing and it is hoped that the SMA approach would be available in the near future as an indigenously developed injectable intra-vasal male contraceptive. The safety and efficacy of available oral contraceptives were evaluated. An indigenously developed oral contraceptive 'Centchorman', which is a nonsteroidal, weakly estrogenic but potently antiestrogenic, was found to be safe and effective and is now being marketed in India since 1991 as a 'once a week' pill. Cyclofem and Mesigyna have been recommended as injectable contraceptives with proper counselling and service delivery by Indian studies. It has been recommended that these injectable contraceptives be added to the existing range of contraceptive methods available in the National Family Planning Programme. Based on the Indian studies CuT 200 was also recommended. Studies have indicated the advantage of intrauterine devices (IUD); they are long acting, relatively easily removed and fertility returns rapidly after their removal. Recent studies have recommended CuT 200 for use up to 5 years. The combination of some plant products i.e. Embelia ribes, Borax and Piper longum has been found to be safe and effective as a female contraceptive and the results of phase-I clinical trials are encouraging. Research work is going on in the country in various areas with special reference to hormonal contraceptive - a three monthly injectable contraceptive, immuno-contraceptives, antiprogestins, etc.


Assuntos
Anticoncepção/estatística & dados numéricos , Norgestrel/análogos & derivados , Animais , Ensaios Clínicos como Assunto , Anticoncepção/métodos , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Masculinos/administração & dosagem , Dispositivos Anticoncepcionais Femininos/estatística & dados numéricos , Dispositivos Anticoncepcionais Masculinos/estatística & dados numéricos , Feminino , Antagonistas de Hormônios/administração & dosagem , Humanos , Índia , Masculino , Norgestrel/administração & dosagem , Extratos Vegetais/administração & dosagem , Plantas Medicinais , Gravidez , Vacinas Conjugadas/administração & dosagem
5.
J Androl ; 21(6): 833-41, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11105909

RESUMO

Rhesus monkeys were used to investigate the role of androgenic steroids and estradiol in the induction of hyperplastic changes in stromal and glandular prostate tissues. Adult male rhesus monkeys were procured from the wild and, after routine quarantine procedures, were randomly divided into 5 groups of 5 animals each. Gluteus maximus muscles were injected with 2.5 mg of androstenedione (Group II), 2.5 mg of dihydrotestosterone (DHT) or 0.25 mg of estradiol (Group II), 2.5 mg androstanediol (Diol; Group IV), or Diol in combination with 0.25 mg of estradiol (Group V). Group I consisted of untreated controls. Animals were injected with steroids 3 times a week for 2 years. Treatment with androstenedione (Group II) resulted in stromal hyperplasia in the caudal lobe and an increase in epithelial cell height in all zones except in the central zone of the caudal lobe. In monkeys treated with DHT and estradiol (Group III), stromal hyperplasia in both lobes, a decrease in tubular size, and degranulation and vacuolation of epithelial cells were noticed. Injection of Diol alone (Group IV) or in combination with estradiol (Group V) resulted in a widening of stroma in the central and peripheral zones of cranial and caudal lobes, whereas the tubular size decreased. Diol also induced epithelial cell hypercellularity in the central and peripheral zones of the caudal lobe and in the peripheral zone of the cranial lobe. Prostate-specific antigen levels in Group IV animals gradually increased from 6 months of treatment and were maximal after 18 months of injections. Serum estradiol levels increased to detectable levels in all groups except Group IV. Serum testosterone levels decreased to very low or undetectable levels in all groups, whereas prostate-specific acid phosphatase increased in all treated groups. Prolactin levels were elevated in all treated groups except in animals injected with androstenedione. These results indicate that repeated long-term injections of androstenedione or DHT and estradiol induced stromal hyperplasia, which may be an estrogen-related effect. Androstanediol-induced hypercellularity and stratification of glandular epithelium is comparable to human prostatic intraepithelial neoplasia. These results also suggest that the rhesus monkey is a suitable animal model for experimental induction of prostate diseases.


Assuntos
Androstano-3,17-diol/farmacologia , Androstenodiona/farmacologia , Di-Hidrotestosterona/farmacologia , Estradiol/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/fisiopatologia , Androstano-3,17-diol/administração & dosagem , Androstenodiona/administração & dosagem , Animais , Tamanho Celular , Di-Hidrotestosterona/administração & dosagem , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Estradiol/administração & dosagem , Humanos , Injeções Intravenosas , Macaca mulatta , Masculino , Próstata/patologia , Próstata/fisiologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia
6.
Endocr Res ; 26(3): 411-29, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11019905

RESUMO

The stimulatory and inhibitory effects on testicular steroidogenesis of transient neonatal hypothyroidism from day 1 postpartum through different postnatal developmental events on testis at puberal age (60 days old) were studied in vivo. Hypothyroidism was induced in neonates by feeding the lactating mother or directly with 0.05% methimazole (MMI) through drinking water from the day of parturition to 10, 15, 30, 40 and 60 days, and were killed at day 60 postpartum. Plasma and testicular interstitial fluid (TIF) progesterone, testosterone, dihydrotestosterone (DHT) and estradiol concentrations were assessed. Testis weight and volume significantly increased in rats subjected to 10 and 15 days of hypothyroidism, decreased in rats subjected to 30, 40 and 60 days of hypothyroidism. A consistent increase in Leydig cell number was seen in puberal rats subjected to transient neonatal hypothyroidism but decreased in 60 days hypothyroid rats. Peritubular myoid cell number was consistently decreased in all experimental rats. Leydig cell diameter decreased consistently in all experimental groups. Persistent hypothyroidism (60 days hypothyroid) consistently decreased both plasma and TIF sex steroids. In transient hypothyroid rats, progesterone concentration decreased in both plasma and TIF. Transient hypothyroidism from birth to day 10 postnatal age maintained normal titre of plasma testosterone, whereas a significant increase in TIF testosterone concentration was evident when compared with controls. All other groups of rats subjected to transient neonatal hypothyroidism had consistently low titres of plasma and TIF testosterone. Plasma DHT concentrations in rats subjected to transient neonatal hypothyroidism remained unaltered. However, TIF DHT increased in 10 days


Assuntos
Animais Recém-Nascidos , Hormônios Esteroides Gonadais/sangue , Hormônios Esteroides Gonadais/metabolismo , Hipotireoidismo/metabolismo , Maturidade Sexual , Testículo/metabolismo , Animais , Contagem de Células , Di-Hidrotestosterona/sangue , Estradiol/sangue , Hipotireoidismo/sangue , Hipotireoidismo/patologia , Células Intersticiais do Testículo , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão , Progesterona/sangue , Ratos , Testículo/patologia , Testosterona/sangue , Tireotropina/sangue , Tiroxina/sangue , Fatores de Tempo , Tri-Iodotironina/sangue
7.
Int J Androl ; 23(2): 95-105, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10762435

RESUMO

Levonorgestrel butanoate, 0.25, 1.0 and 2.5 mg/kg, administered as two injections 60 days apart (groups II, III, IV), failed to suppress spermatogenesis consistently and uniformly in adult bonnet monkeys (group size, n=6) compared to controls (group I). Levonorgestrel butanoate at the same doses combined with two simultaneous injections of 40 mg testosterone buciclate (groups V, VI, VII), consistently suppressed spermatogenesis in the period 60-240 days and in most animals to azoospermia or severe oligozoospermia (<5 x 106/mL) during days 90-210. The degree and duration of suppression were greatest in group VI. Sperm motility declined in all treated animals and spermatozoa in the semen of animals from groups V and VI lost all progressive motility in the period 60-150 and 60-210 days, respectively. The changes in testosterone levels were similar in groups V and VI, increasing within 24 h after the combined injection to reach a peak by day 28 followed by a sharp decrease until day 67. The second injection increased testosterone levels by a lesser degree to peak levels on day 81. In group VII, testosterone levels decreased until day 59 after the first injection but increased to a maximum on day 81 after the second injection followed by a gradual decrease until day 150 to below baseline values. Peak levels of serum levonorgestrel were observed 1-7 days after injection of levonorgestrel butanoate alone. Clearance of the drug was slow, being detectable in the circulation until day 330 of the 360 day study period in the high dose group. Dose-response increases to peak levels of levonorgestrel were attained on day 7 in groups V, VI and VII, after the first injection. After the second injection, peak levels were seen on day 61 in groups V and VI and on day 81 in group VII. Levonorgestrel was no longer detectable in blood in groups V and VI by days 210 and 300, respectively, but small circulating amounts remained in group VII at the conclusion of the study on day 360. This study indicates that when levonorgestrel butanoate is combined with a long-acting androgen and injected at two-monthly intervals, effective and reversible suppression of spermatogenesis is achieved.


Assuntos
Norgestrel/análogos & derivados , Espermatogênese/efeitos dos fármacos , Testosterona/análogos & derivados , Animais , Peso Corporal/efeitos dos fármacos , Macaca radiata , Masculino , Norgestrel/farmacologia , Sêmen/efeitos dos fármacos , Contagem de Espermatozoides/efeitos dos fármacos , Motilidade Espermática/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testosterona/farmacologia
8.
Endocr Res ; 25(3-4): 323-40, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10596726

RESUMO

The impact of transient neonatal hypothyroidism on growth and function of puberal testis during different milestones of postnatal testicular development was studied in Wistar rats. Rat pups were made hypothyroid for 10, 15, 30, 40 and 60 days of postnatal age from birth by providing 0.05% (W/V) methimazole (MMI) in the drinking water of the mother, from day 1 postpartum till weaning (25 days postpartum) and thereafter in the drinking water. Control rats were raised without MMI treatment. Sertoli cell number and its function was assessed on day 60 postpartum. Sertoli cell number increased consistently in 10, 15, 30 and 40 days transient hypothyroid rats but decreased in rats subjected to continuous hypothyroidism from birth to 60 days postpartum. Rats subjected to continuous hypothyroidism from birth showed spermatogenic arrest at puberty and had only a single layer of spermatogonia. Transient neonatal hypothyroidism for 10 (or) 15 days from birth increased spermatocytes (pachytene and zygotene), spermatids (elongated and round) whereas, that of 30 and 40 days decreases the number of germ cells. Plasma androgen binding protein (ABP) concentration decreased in puberal rats belonging to all groups, whereas the testicular interstitial fluid (TIF) concentration of ABP increased significantly in 10 and 15 days hypothyroid rats while it decreased in all other groups. These findings indicate that the mitogenic activity of Sertoli cell is increased irrespective of the duration of transient neonatal hypothyroidism. However, the functional activity of Sertoli cells (ABP production) in these puberal rats varies depending upon the postnatal period at which the animals were in hypothyroid state.


Assuntos
Proteína de Ligação a Androgênios/metabolismo , Animais Recém-Nascidos , Hipotireoidismo/patologia , Células de Sertoli/patologia , Contagem de Espermatozoides , Testículo/metabolismo , Envelhecimento , Proteína de Ligação a Androgênios/sangue , Animais , Contagem de Células , Espaço Extracelular/metabolismo , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/metabolismo , Masculino , Metimazol , Tamanho do Órgão , Ratos , Ratos Wistar , Túbulos Seminíferos/patologia , Espermátides , Espermatócitos , Testículo/patologia , Hormônios Tireóideos/sangue , Fatores de Tempo
9.
J Endocrinol ; 162(3): 443-50, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10467236

RESUMO

Rhesus monkey prostate epithelial cells from the cranial lobe were isolated and cultured in flasks coated either with collagen IV or laminin. The effects of stromal cell medium, androgens and growth factors on cell number, thymidine incorporation and secretory activity were assessed. The results indicate that dihydrotestosterone (DHT) and androstenedione have stimulatory influences on cell proliferation and secretion in coated flasks. DHT was more effective in increasing cell number but the induction of secretory activity was similar with both steroids. The combination of IGF-I and -II resulted in inducing better cell proliferation and secretory activity than the individual IGFs but, of the two IGFs, IGF-I was more effective than IGF-II. DHT with IGFs was more potent in inducing proliferation, differentiation and secretion than androstenedione. Even in the absence of steroids or growth factors, colony formation and confluence occurred in coated flasks but cell differentiation and secretion only to a limited extent. In conclusion, we were able to establish an in vitro primary culture of prostate epithelial cells from rhesus monkey using extracellular matrix proteins, steroids and growth factors as additional supplements. This culture system may be useful to study prostate cell physiology and to identify drugs that can inhibit cell proliferation.


Assuntos
Androgênios/farmacologia , Células Epiteliais/citologia , Próstata/citologia , Somatomedinas/farmacologia , Fosfatase Ácida/análise , Androstenodiona/farmacologia , Animais , Técnicas de Cultura de Células , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Di-Hidrotestosterona/farmacologia , Células Epiteliais/química , Células Epiteliais/efeitos dos fármacos , Proteínas da Matriz Extracelular/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like II/farmacologia , Macaca mulatta , Masculino , Próstata/química , Próstata/efeitos dos fármacos , Antígeno Prostático Específico/análise
10.
Contraception ; 59(5): 333-7, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10494487

RESUMO

The effects of long term administration of testosterone enanthate (TE) on glucose metabolism including glucose tolerance test (GTT) and fasting serum insulin levels were evaluated in adult rhesus monkeys kept under controlled dietary conditions. Adult male rhesus monkeys (n = 9) were administered 50 mg of TE bimonthly for 32 months, whereas control animals were injected the vehicle only. Glucose concentration reached a maximum 5 min after an intravenous glucose load and thereafter decreased gradually to reach near baseline values within 60 min. Significant changes in GTT or t1/2 of glucose were not seen in animals treated with TE, throughout the treatment period. However, serum insulin levels decreased significantly from months 27-32 of TE treatment and returned to baseline values within 3 months of recovery.


Assuntos
Glicemia/metabolismo , Testosterona/análogos & derivados , Animais , Glicemia/efeitos dos fármacos , Esquema de Medicação , Jejum , Teste de Tolerância a Glucose , Insulina/sangue , Macaca mulatta , Masculino , Testosterona/sangue , Testosterona/farmacologia , Fatores de Tempo
11.
Int J Androl ; 22(6): 347-55, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10624603

RESUMO

The present study was designed to evaluate the effects of long-term administration of testosterone enanthate (TE) on lipid and liver function parameters in rhesus monkeys (n = 9) maintained under controlled dietary conditions. Bimonthly administration of 50 mg of TE increased serum testosterone into the supraphysiological range one day after injection and peak levels were seen on day 3, followed by a decrease to above baseline values by day 14. High density lipoprotein cholesterol (HDL-C) levels decreased gradually; compared to baseline values, the decline was significant from the 19th month of injection until the first month of recovery. The increase in low density lipoprotein cholesterol (LDL-C) levels and the LDL-C/HDL-C ratio during the treatment period was not significant compared to baseline values; however, when compared to control animals, HDL-C and LDL-C levels and the LDL-C/HDL-C ratio were significantly elevated from the 12th month until the end of the treatment period. All lipid parameters recovered by the end of the treatment period. Control animals (n = 9) did not show significant changes in HDL-C and LDL-C levels and the LDL-C/HDL-C ratio during the study period. Total cholesterol levels decreased in control (n = 9) and treated animals from 6 to 15th months of the treatment period, coinciding with the feeding of sprouted grams to animals. TE injections did not change the levels of triglycerides, alkaline phosphatase or bilirubin in control and treated animals. However, transaminase (SGOT and SGPT) levels increased following TE injections and remained elevated until the end of injections followed by a return to baseline values or below during the recovery period. These effects could be due to the pharmacokinetic profile of TE in which testosterone levels were elevated to supraphysiological values after injections. The recovery of the TE-induced changes in lipid parameters and liver transminases is reassuring but the changes in these parameters during TE injections indicate the need for long-acting androgens with better pharmacokinetic properties.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Anticoncepcionais Masculinos/farmacologia , Lipídeos/sangue , Fígado/efeitos dos fármacos , Testosterona/análogos & derivados , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Peso Corporal , Colesterol/sangue , Anticoncepcionais Masculinos/administração & dosagem , Anticoncepcionais Masculinos/efeitos adversos , Fígado/fisiopatologia , Testes de Função Hepática , Macaca mulatta , Masculino , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Testosterona/sangue , Testosterona/farmacologia , Fatores de Tempo , Triglicerídeos/sangue
12.
Indian J Exp Biol ; 29(12): 1140-1, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1816100

RESUMO

Administration of testosterone propionate (TP; 1 mg/kg body weight/day; im, for 30 days) to mature male bonnet monkeys, decreased total lipids, glyceride glycerol and cholesterol concentrations in hepatic tissue. The decrease in glyceride glycerol was due to decrease in monoacyl and triacyl glycerol. Both, free and esterified cholesterol were decreased after testosterone administration. Eventhough, total phospholipid was not significantly altered, phosphatidylserine and cardiolipin were increased, due to testosterone administration. Testosterone inhibited NADP-isocitrate dehydrogenase activity in liver. The findings suggest that testosterone acts as a lipolytic hormone and its action may be direct through its specific receptors in liver.


Assuntos
Metabolismo dos Lipídeos , Fígado/metabolismo , Testosterona/fisiologia , Animais , Macaca radiata , Masculino
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