RESUMO
Epidemiological and in vitro data have not provided conclusive evidence concerning the involvement of thyroid hormones (THs) on mammary carcinogenesis. We used an in vivo model to assess the relationship between THs, adipose tissue and breast cancer development. Female SpragueDawley rats were treated with a dose of 7,12-dimethylbenz(a)anthracene (15 mg/rat) at 55 days of age and were then divided into four experimental groups: hypothyroid rats (HypoT, 0.01% 6-N-propyl-2-thiouracil in drinking water), untreated control (EUT); hyperthyroid rats (HyperT, 0.25 mg/kg/day T4 s.c.) and vehicle-treated control rats. The latency of tumor appearance and the incidence and progression of tumors were determined. At sacrifice, blood samples were collected for hormone determinations and samples of tumor and mammary glands were obtained for immunohistological studies. HypoT rats had retarded growth and an increase in mammary fat. The latency was longer (p<0.0001), the incidence rate was lower (p<0.05) and tumor growth was slower in HypoT rats compared to EUT and HyperT rats. Mitotic index and PCNA immunostaining were similar in all groups. HypoT rats showed increased apoptosis (p<0.05) as evaluated by the apoptotic index and TUNEL staining. No differences in serum prolactin and progesterone were observed. However, circulating estradiol (E2) was significantly lower in HypoT and HyperT rats. Serum leptin levels were reduced in HypoT rats even though the abdominal fat mass was similar in all groups. To note, the leptin level was higher in HypoT rats that developed mammary tumors than the level in non-tumoral HypoT rats. In conclusion, hypothyroidism altered animal growth, breast morphology, body composition, leptin secretion and serum E2 enhancing apoptosis and, consequently, retarding mammary carcinogenesis in rats.
Assuntos
Apoptose/fisiologia , Hipotireoidismo/metabolismo , Glândulas Mamárias Animais/metabolismo , Neoplasias Mamárias Experimentais/metabolismo , 9,10-Dimetil-1,2-benzantraceno , Adipocinas/metabolismo , Animais , Composição Corporal , Carcinógenos , Proliferação de Células , Estradiol/sangue , Feminino , Leptina/sangue , Glândulas Mamárias Animais/efeitos dos fármacos , Progesterona/sangue , Prolactina/sangue , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVES: To determine whether lower serum prostate-specific antigen (PSA) concentration in obese men is caused by plasma hemodilution and/or decreased serum testosterone levels. METHODS: A sample of 413 men, from 45 to 75 years old, were randomly selected for the study among those who participated in prostate cancer screening at 2 urban urology practices in Argentina and Puerto Rico. Weight, height, serum testosterone and total PSA concentration were determined. Body mass index (BMI), body surface, plasma volume, and PSA mass were calculated. Prostate volume was estimated by transrectal ultrasound using the prolate ellipsoid formula. RESULTS: Mean age was 59 years old (range, 45 to 75) and mean BMI was 28.8 kg/m2 (range, 24 to 46). Mean serum PSA concentration was 1.43 ng/ml in normal weight patients (n=68), 1.4 ng/ml in overweight patients (n=222), 1.05 ng/ml in obese patients (n=114), and 0.85 ng/ml in morbidly obese patients (n=9). BMI was directly correlated with plasma volume (r= 0.687; p= 0.001) and inversely correlated with serum PSA concentration (r= -0.235; P= 0.001). PSA mass tended to be lower in obese and morbidly obese patients (P= 0.0063)compared to normal weight and overweight subjects. Serum testosterone concentration (P= 0.91) and prostate volume (P= 0.068) were similar among all BMI groups. CONCLUSIONS: Obese men had lower serum PSA concentrations than normal weight men mainly due to plasma hemodilution. PSA mass tended to be lower in obese patients, but it is unlikely a consequence of lower serum testosterone concentrations.