Circulating oxidative stress parameters in pre- and post-menopausal healthy women and in women suffering from breast cancer treated or not with neoadjuvant chemotherapy.

We evaluate here the redox status in pre- and post-menopausal healthy women and in women with breast cancer in order to understand the consequences of the hormonal alterations of menopause for the oxidative stress status, its modifications with breast cancer and the influence of neoadjuvant chemotherapy (NC). To that, serum oxidative stress parameters (total antioxidant capacity, lipid peroxidation and protein oxidation), non-enzyme antioxidant defenses (total glutathione, uric acid and bilirubin) and enzyme antioxidant defenses (superoxide dismutase, catalase and glutathione peroxidase activities) were measured in healthy women and in women with breast cancer divided according to their menopausal status and that received or not NC. Circulating estradiol, progesterone, FSH and LH were also analyzed. We found that menopause itself modifies the redox status of healthy women, being most of these differences also reflected in women with breast cancer. However, several changes occur as a consequence of the disease. Furthermore, NC increases oxidative damage, decreases antioxidant defenses and eliminates the differences found in menopause. We conclude that the normal redox balance is disrupted by breast cancer but is also affected by the hormonal status promoted by menopause. In fact, NC nullifies the differences found between pre- and postmenopausal women in several antioxidant defense systems.

Serum specific vasopressin-degrading activity is related to blood total cholesterol levels in men but not in women.

The role of vasopressin (AVP) in the pathophysiology of cardiovascular disease is controversial, but this peptide hormone is elevated in heart failure and some forms of hypertension. Also, AVP has vasoconstrictor, mitogenic, hyperplasic and renal fluid retaining properties which, by analogy with angiotensin II, may have deleterious effects when present in chronic excess. Furthermore, cholesterol blood levels are also associated with hypertension, although the underlying mechanism is not known. Here we analyze the relationship between blood total cholesterol levels and serum vasopressin- degrading cystyl-aminopeptidase activity (AVP-DA) in healthy humans, and the differences between men and women. Linear correlation coefficients were calculated to test relationships between AVP-DA and blood total cholesterol levels. Sex differences were observed for AVP-DA, being this activity higher in men than in women. According to the linear model of the regression analysis, AVP-DA showed a significant negative correlation with blood total cholesterol levels in men, whereas no correlation was observed in women. Several studies in humans demonstrate the existence of greater plasma AVP concentrations in normal men compared to normal women, which could explain the gender-differences observed in the present work in relation with AVP-DA. However, AVP-DA is related to blood cholesterol levels only in men, although in our hands, women showed higher blood cholesterol levels than men. This could indicate that the risk of high cholesterol-related hypertension is more probable in men than in women. Although AVP-DA misregulation could be involved in the pathogenesis of hypertension, its relation with cholesterol levels appears only in men, but not in women.

Hypothalamus-pituitary-thyroid axis disruption in rats with breast cancer is related to an altered endogenous oxytocin/insulin-regulated aminopeptidase (IRAP) system.

Associations of breast cancer with diseases of the thyroid have been repeatedly reported, but the mechanism underlying this association remains to be elucidated. It has been reported that oxytocin (OXT) attenuates the thyroid-stimulating hormone (TSH) release in response to thyrotrophin-releasing hormone (TRH) and decreased plasma levels of TSH as well as the thyroid hormones by an effect mediated by the central nervous system. Oxytocinase (IRAP) is the regulatory proteolytic enzyme reported to hydrolyze OXT. Changes in IRAP activity have been reported in both human breast cancer and N-methyl-nitrosourea (NMU)-induced rat mammary tumours. Here, we measure IRAP activity fluorometrically using cystyl-ß-naphthylamide as the substrate, in the hypothalamus-pituitary-thyroid axis together with the circulating levels of OXT, and its relationship with circulating levels of TSH and free thyroxine (fT4), as markers of thyroid function in control rats and rats with breast cancer induced by NMU. We found decreased thyroid function in rats with breast cancer induced by NMU, supported by the existence of lower serum circulating levels of both TSH and fT4 than their corresponding controls. Concomitantly, we found a decrease of hypothalamic IRAP activity and an increase in circulating levels of OXT. We propose that breast cancer increases OXT pituitary release by decreasing its hypothalamic catabolism through IRAP activity, probably due to the alteration of the estrogenic endocrine status. Thus, high circulating levels of OXT decreased TSH release from the pituitary, and therefore, of thyroid hormones from the thyroid, supporting the association between breast cancer and thyroid function disruption.

Doxazosin blockade of alpha 1-adrenergic receptors increases rat serum progesterone levels: a putative role of ovarian angiotensin III in steroidogenesis.

OBJECTIVE: To analyze the role of the local renin-angiotensin system (RAS) in the female reproductive system to modulate ovarian steroidogenesis and its relationship with alpha(1)adrenergic receptors. DESIGN: Observational study. SETTING: University laboratory. ANIMAL(S): Adult female Wistar rats treated with doxazosin (10 mg/kg) or vehicle for 15 days. INTERVENTION(S): Samples from the whole right ovary were dissected after perfusion with saline. The soluble and membrane-bound fractions were obtained from these samples. Also, blood samples were used to obtain the serum. MAIN OUTCOME MEASURE(S): Fluorometric measurement of soluble and membrane-bound RAS-regulating proteolytic regulatory enzyme activities by using arylamide derivatives as substrates. Time-resolved fluoroimmunoassay of serum E(2) and P. RESULT(S): alpha(1)Adrenergic receptor blockade increases ovarian soluble and membrane-bound aminopeptidase A and decreases membrane-bound aminopeptidase N and aminopeptidase B. Furthermore, serum P levels increased, whereas serum E(2) did not change. CONCLUSION(S): Ovarian P production, at least in the rat, is regulated by noradrenaline through a mechanism of action in which the RAS is involved, with a main role for angiotensin III.