Literature DB >> 15497689

Tamoxifen alters hepatic cytochrome P450 enzyme expression and circulating growth hormone levels in intact male rats.

Ludger M Ickenstein1, Susan L Holsmer, Stelvio M Bandiera.   

Abstract

PURPOSE: To investigate the effects of acute tamoxifen treatment on hepatic cytochrome P450 (CYP) expression and circulating thyroid and growth hormone (GH) levels in intact adult male rats.
METHODS: Rats were injected subcutaneously with peanut oil (vehicle) or tamoxifen at a dosage of 20 or 200 mg/kg for 2 consecutive days. Blood for GH measurements was collected on day 34. Rats were sacrificed at 37 days after treatment, trunk blood was collected, and hepatic microsomes were prepared.
RESULTS: Mean body weight of rats treated with tamoxifen at 200 mg/kg was decreased compared to vehicle-treated rats throughout the 5-week period after treatment. Hepatic CYP2A1-dependent testosterone 7alpha-hydroxylase activity and CYP2A1 protein content were increased, whereas CYP2C11-mediated testosterone 2alpha- and 16alpha-hydroxylase activities and CYP2C11 protein content were decreased significantly following tamoxifen administration. Peak plasma GH levels were 60% lower and nadir plasma GH levels were 30% higher in tamoxifen-treated relative to vehicle-treated rats. In contrast, serum triiodothyronine and thyroxine levels were not affected by tamoxifen treatment.
CONCLUSIONS: Hepatic CYP enzyme expression was altered and body weight was decreased in adult male rats 5 weeks after treatment with tamoxifen. This alteration corresponded to changes in plasma GH levels.

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Year:  2004        PMID: 15497689     DOI: 10.1023/b:pham.0000041458.81836.c4

Source DB:  PubMed          Journal:  Pharm Res        ISSN: 0724-8741            Impact factor:   4.200


  29 in total

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Authors:  T OMURA; R SATO
Journal:  J Biol Chem       Date:  1964-07       Impact factor: 5.157

Review 2.  Antiestrogens and selective estrogen receptor modulators as multifunctional medicines. 2. Clinical considerations and new agents.

Authors:  V Craig Jordan
Journal:  J Med Chem       Date:  2003-03-27       Impact factor: 7.446

3.  Female-predominant rat hepatic P-450 forms j (IIE1) and 3 (IIA1) are under hormonal regulatory controls distinct from those of the sex-specific P-450 forms.

Authors:  D J Waxman; J J Morrissey; G A LeBlanc
Journal:  Endocrinology       Date:  1989-06       Impact factor: 4.736

4.  Sex hormones in postmenopausal women with breast cancer on tamoxifen.

Authors:  I Kostoglou-Athanassiou; K Ntalles; J Gogas; C Markopoulos; V Alevizou-Terzaki; P Athanassiou; E Georgiou; C Proukakis
Journal:  Horm Res       Date:  1997

5.  Neonatal low- and high-dose exposure to estradiol benzoate in the male rat: II. Effects on male puberty and the reproductive tract.

Authors:  O Putz; C B Schwartz; G A LeBlanc; R L Cooper; G S Prins
Journal:  Biol Reprod       Date:  2001-11       Impact factor: 4.285

6.  Thyroid function test changes with adjuvant tamoxifen therapy in postmenopausal women with breast cancer.

Authors:  C C Mamby; R R Love; K E Lee
Journal:  J Clin Oncol       Date:  1995-04       Impact factor: 44.544

7.  Tamoxifen attenuates pulsatile growth hormone secretion: mediation in part by somatostatin.

Authors:  G S Tannenbaum; W Gurd; M Lapointe; M Pollak
Journal:  Endocrinology       Date:  1992-06       Impact factor: 4.736

8.  Modulation of hepatic level of microsomal testosterone 7 alpha-hydroxylase, P-450a (P450IIA), by thyroid hormone and growth hormone in rat liver.

Authors:  Y Yamazoe; X Ling; N Murayama; D Gong; K Nagata; R Kato
Journal:  J Biochem       Date:  1990-10       Impact factor: 3.387

9.  Estrogen receptor blockade with tamoxifen diminishes growth hormone secretion in boys: evidence for a stimulatory role of endogenous estrogens during male adolescence.

Authors:  D L Metzger; J R Kerrigan
Journal:  J Clin Endocrinol Metab       Date:  1994-08       Impact factor: 5.958

10.  Long term effects of tamoxifen. Biological effects of Tamoxifen Working Party.

Authors:  J Cuzick; D Allen; M Baum; J Barrett; G Clark; V Kakkar; E Melissari; C Moniz; J Moore; V Parsons
Journal:  Eur J Cancer       Date:  1992       Impact factor: 9.162

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  1 in total

1.  Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat.

Authors:  Noel N Kim; Miljan Stankovic; Abdullah Armagan; Tulay T Cushman; Irwin Goldstein; Abdulmaged M Traish
Journal:  BMC Womens Health       Date:  2006-09-13       Impact factor: 2.809

  1 in total

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