Experimental hypothyroidism increases apoptosis in dimethylbenzanthracene-induced mammary tumors.

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.

Obesity modifies prostatic specific antigen in men over 45 years.

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.

La obesidad modifica el antígeno prostático específico en hombres mayores de 45 años de edad / Obesity modifies prostatic specific antigen in men over 45 year

OBJETIVO: Determinar si las menores concentraciones séricas de antígeno prostático específico (PSA) encontradas en los sujetos obesos son consecuencia de bajos niveles de testosterona circulante y/o del mayor volumen plasmático (-VP- hemodilución).MÉTODOS: Fueron seleccionados 413 individuos de sexo masculino entre 45 y 75 años. El trabajo consistió en una evaluación de la composición corporal mediante antropometría (medición de peso y talla y cálculo del índice de masa corporal –IMC-, superficie corporal- SC- y VP), estimación de peso prostático por ecografía transrectal (ETR) y un análisis de laboratorio incluyendo dosaje de la PSA total y, en un subgrupo de pacientes (n= 108), determinación de la concentración sérica de testosterona. Se calculó la masa de PSA circulante (PSA masa). El análisis estadístico se realizó mediante Anova I y el coeficiente de correlación de Pearson (p<0.05).RESULTADOS: La edad promedio fue de 59,08 años y la media de IMC de 28,80 kg/m2. Los sujetos con IMC entre 20-24,9 kg/m2 (n= 68) presentaron una media de PSA de 1,43 ng/ml; en los voluntarios con sobrepeso (n=222), IMC entre 25-29,9 kg/m2, la media encontrada de fue de 1,40 ng/ml; en los obesos tipo I (n=114), IMC entre 30-39,9 kg/m2, se halló una PSA media de 1,05 ng/ml y finalmente en los obesos tipo II (n= 9), IMC > 40 kg/m2 , el PSA tuvo un valor medio de 0,85 ng/ml. Un mayor IMC se asoció significativamente con un mayor VP (r= 0,687; p =0,001) y con una menor concentración sérica de PSA (r= -0,235; p= 0,001). Por su parte, el PSA masa fue menor en los pacientes obesos tipo I y II que en los voluntarios con sobrepeso y normopeso aunque estadísticamente no significativo ( p<0.063). El peso prostático y los niveles de testosterona fueron similares en todos los voluntarios independientemente del estado nutricional que presentaran(AU)

CONCLUSIÓN: La principal causa de menor concentración de PSA en sujetos obesos sería la hemodilución por mayor volumen plasmático; sin embargo, también hay una discreta reducción en la secreción de proteína PSA en estos sujetos aunque no estaría relacionada bajos niveles de testosterona(AU)

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(AU)