Aging is associated with insulin resistance, which represents a common factor in age-related diseases. We aimed to determine the role of 17beta-estradiol on insulin sensitivity and memory during aging using ovariectomized rats (2-26 months of age) treated with physiological doses of 17beta-estradiol. Our results indicate a lack of effect of 17beta-estradiol replacement on spatial memory assessed in a water maze. Conversely, estradiol treatment improved insulin sensitivity in aging rats. These data imply that relatively low doses of 17beta-estradiol may have beneficial effects on glucose homeostasis due to the protective effects of estrogen. However, estradiol treatment used in the present study did not prevent memory impairment associated with aging.

Aging is associated with a reduction in metabolic function, insulin resistance, increased incidence of neurodegenerative diseases, and memory or cognitive dysfunction. In aging females, loss of gonadal function determines the beginning of the period of reduced metabolic function. Estrogens have neuroprotective effects, but the mechanisms by which they exert these effects remain unclear. The effects of estradiol treatment on the activation of the insulin receptor substrate (IRS)-1 signaling pathway, the interactions between estrogen receptor (ER)-alpha and IRS-1 and the p85alpha subunit of phosphatidylinositol-3 kinase, together with the possible effects of estradiol treatment on glucose transporter-3 and -4 levels, were investigated in female rats. The level of expression of each glucose transporter was greater in control and estradiol-treated groups than in the ovariectomized group. Interactions of ERalpha46-IRS-1, ERalpha46-p85alpha, and p85alpha-IRS-1, as well as IRS-1 phosphorylation, appeared to increase with estradiol treatment. The results indicate that estradiol treatment improves some aspects of neuronal homeostasis that are affected by aging; this may indicate that estradiol has neuroprotective effects in female rats. Additional animal studies are required to clarify the neuroprotective role of estradiol in relation to other important molecules involved in the IRS-1-phosphatidylinositol-3 kinase signaling pathway.

These observations show that the human Fallopian tube expresses PAFr and PAF-AH at a location compatible with the proposed paracrine role of early embryo-derived PAF.

It has been reported that in streptozotocin (STZ)-induced diabetes, hyperglycaemia leads to progressive insulin resistance of the peripheral tissues. In this study, we tried to elucidate the effects of hyperglycaemia on insulin sensitivity and insulin signalling in ovariectomized (STZ)-induced diabetic rats. In addition, we attempted to demonstrate the role of 17β-oestradiol and progesterone on insulin sensitivity, focusing on their effects on key proteins of skeletal muscle, insulin receptor (IR) and glucose transporter-4 (Glut-4). Our results show that hyperglycaemia could modulate insulin signalling, at the IR and Glut-4 level, in different ways depending on exposure time. 17β-Oestradiol and progesterone have different effects on insulin signalling. 17β-Oestradiol treatment improves insulin sensitivity, but its action is dependent on the exposure time and its plasma level. During the early period of treatment (days 6-11), this hormone counteracts the effects of hyperglycaemia downstream of the IR, whereas during the later period of treatment (days 11-16), it may counteract the effects of hyperglycaemia by modulating IR relative tyrosine phosphorylation. By contrast, progesterone only improves insulin sensitivity during the early period of treatment (days 6-11), and this effect is not associated with changes in IR and Glut-4 content. Both hormones have a protective role in skeletal muscle against the effects of glucose toxicity, but their effects begin at different stages of treatment. These new findings improve our understanding of insulin resistance in type 1 diabetes mellitus and of the risk/benefit ratio when 17β-oestradiol and progesterone are used in oral contraceptives or hormone replacement therapy taken by menopausal women with controlled type 1 diabetes mellitus.

Interaction of Neisseria gonorrhoeae with the oviductal epithelium in vitro was examined in 2 cm length segments obtained after surgical sterilization from users of copper T intrauterine device (IUD) or Norplant and control women. Segments perfused with N.gonorrhoeae suspensions were incubated from 30 min up to 4 h, fixed, frozen and cut in 6--10 microm sections. Bacteria were detected immunohistochemically with rabbit anti-gonococcal serum followed by light and confocal microscopy. Adhesion and internalization of gonococci by epithelial cells were observed at all incubation times, and both were higher in explants from users of copper T IUD or Norplant implants than controls. The epithelium of controls expressed CD66 and syndecan-1; but CD46 was found in only one out of six cases. The epithelium of copper T IUD users expressed CD66 but not syndecan-1 or CD46. Users of Norplant exhibited expression of CD46, CD66 and syndecan-1. Label was always found along the luminal border of the epithelium. There were more intraepithelial lymphocytes in users of contraceptive methods than in controls. Results indicate that (i) N.gonorrhoeae invade the oviductal epithelium from the first minutes of exposure, (ii) the epithelium is constitutively endowed with two known receptors for the gonococcus, CD66 and syndecan-1, (iii) copper T IUD and Norplant users exhibit higher rates of attachment and internalization of the gonococcus into the oviductal epithelium associated with changes in expression of gonococcal receptors.