Severe insulin resistance is a key abnormality in obese women with polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate whether pioglitazone decreases insulin resistance (IR) and hyperandrogenism to the same extent as metformin in obese women with PCOS who have not received any previous treatment. Fifty-two women with PCOS were randomly allocated to receive either pioglitazone (30 mg/d, n = 25) or metformin (850 mg three times daily, n = 27) and were assessed before and after 6 months. Body weight, body mass index, and waist to hip ratio increased significantly (P

Although it has been known for many years that the ovary is innervated by catecholaminergic nerve fibers and much experimental evidence has strengthened the notion that catecholamines are physiologically involved in the control of ovarian function, scarce evidence has been presented as to the role of sympathetic activity in ovarian pathologies that affect reproductive function. The purpose of this article is to provide a succinct overview of the findings in this area and discuss them relative to the pathology of polycystic ovary syndrome, the most common ovarian pathology in women during their reproductive years.

Vasoactive intestinal polypeptide (VIP) stimulates estradiol and progesterone release from ovarian granulosa cells in vitro. Very little information is available as to the role VIP plays in the control of steroid secretion during reproductive cyclicity and in ovarian pathologies involving altered steroid secretion. In this study, we determined the involvement of VIP in regulating ovarian androgen and estradiol release during estrous cyclicity and estradiol valerate (EV)-induced polycystic ovarian development in rats. Our findings show that androgen and estradiol release from ovaries obtained during different stages of rat estrous cycle mimic cyclic changes in steroid release observed in vivo with maximal release occurring during late proestrus. VIP increased androgen release from ovaries of all cycle stages except late proestrus and estradiol release from all cycle stages. Increases in VIP-induced androgen and estradiol release were maximal at early proestrus. Inclusion of saturating concentrations of androstenedione increased magnitude of VIP-induced estradiol release at diestrus and estrus but not proestrus. Magnitude of VIP-induced androgen and estradiol release tended to be greater in the ovaries from EV-treated rats with polycystic ovary compared with estrous controls. At the tissue level, ovarian VIP concentration was cycle stage dependent with highest level seen in diestrus. Maximum concentration of VIP was found in EV-treated rats. Changes in VIP were inversely related to changes in ovarian nerve growth factor, a neuropeptide involved in ovarian androgen secretion. These results strongly suggest that intraovarian VIP participates in the control of estradiol secretion during the rat estrous cycle and possibly in the maintenance of increased ovarian estradiol secretory activity of EV-treated rats.

Increasing evidence in animal models and in humans shows that sympathetic nerve activity controls ovarian androgen biosynthesis and follicular development. Thus, sympathetic nerve activity participates in the follicular development and the hyperandrogenism characteristics of polycystic ovary syndrome, which is the most prevalent ovarian pathology in women during their reproductive years. In this study, we mimic sympathetic nerve activity in the rat via "in vivo" stimulation with isoproterenol (ISO), a β-adrenergic receptor agonist, and test for the development of the polycystic ovary condition. We also determine whether this effect can be reversed by the administration of propranolol (PROP), a β-adrenergic receptor antagonist. Rats were treated for 10 days with 125 μg/kg ISO or with ISO plus 5 mg/kg PROP. The ovaries were examined 1 day or 30 days following drug treatment. While ISO was present, the ovaries had an increased capacity to secrete androgens; ISO + PROP reversed this effect on androgen secretory activity. 30 days after treatment, androstenedione secretion reverted to normal levels, but an increase in the intra-ovarian nerve growth factor (NGF) concentration and luteinizing hormone (LH) plasma levels was detected. ISO treatment resulted in follicular development characterized by an increased number of pre-cystic and cystic ovarian follicles; this was reversed in the ISO + PROP group. The lack of change in the plasma levels of progesterone, androstenedione, testosterone, or estradiol and the increased LH plasma levels strongly suggests a local intra-ovarian effect of ISO indicating that β-adrenergic stimulation is a definitive component in the rat polycystic ovary condition.

Reduced activity has been linked to age-associated physiological changes but the underlying root cause is unclear. The goal of the present study was to compare the orexin neuronal system of old (23–29 years) female rhesus macaques with either active or sedentary 24-hour locomotor activity patterns. Using immunohistochemistry we counted the number of orexin A and orexin B neurons in the lateral hypothalamic area (LHA) of each animal. Overall, we observed no difference in the distribution pattern or number of either orexin A or orexin B immune-positive neurons between animals in the two groups. Thus, reduced activity in the elderly is unlikely to stem from a loss of orexin neuronal perikarya in the LHA. This, however, does not rule out the possibility that the reduced activity stems from reduced orexin neuronal projections to arousal centers of the brain, such as the locus coeruleus, or from attenuated release of orexin.

In mammals, the suprachiasmatic nucleus (SCN) is the location of a master circadian pacemaker. It receives photic signals from the environment via the retinal hypothalamic tract, which play a key role in synchronizing the body's endogenously generated circadian rhythms with the 24-h rhythm of the environment. Therefore, it is plausible that age-related changes within the SCN contribute to the etiology of perturbed activity-rest cycles that become prevalent in humans during aging. To test this hypothesis, we used gene arrays and quantitative RT-PCR to profile age-related gene expression changes within the SCN of male rhesus macaques - a pragmatic translational animal model of human aging, which similarly displays an age-related attenuation of daytime activity levels. As expected, the SCN showed high expression of arginine vasopressin, vasoactive intestinal polypeptide, calbindin and nuclear receptor subfamily 1, group D, member 1 (NR1D1) (also known as reverse strand of ERBA (REV-ERBα), both at the mRNA and protein level. However, no obvious difference was detected between the SCNs of young (7-12 years) and old animals (21-26 years), in terms of the expression of core clock genes or genes associated with SCN signaling and neurotransmission. These data demonstrate the resilience of the primate SCN to normal aging, at least at the transcriptional level and, at least in males, suggest that age-related disruption of activity-rest cycles in humans may instead stem from changes within other components of the circadian system, such as desynchronization of subordinate oscillators in other parts of the body.

Dehydroepiandrosterone (DHEA) hormonal supplementation can improve oocyte quality in women with diminished ovarian function. However, it is unclear whether DHEA supplementation can also enhance ovarian function during the perimenopause (i.e., when the number of follicles in the ovary has undergone a marked reduction). To address this question, we examined the impact of 2.5-months of daily 5-mg oral DHEA supplementation on the number of ovarian follicles and the concentrations of anti-Müllerian hormone (AMH) in perimenopausal rhesus macaques. Like women, these long-lived nonhuman primates have ~ 28-day menstrual cycles and eventually undergo menopause. They also show similar age-related neuroendocrine changes, including a marked decrease in circulating concentrations of DHEA and DHEA sulfate (DHEAS). Our experimental design involved the following three groups of animals (N = 6 per group): Young adult (mean age = 11.6 years), Old control (mean age = 23.1 years), and Old DHEA-treated (mean age = 23.5 years). Histological examination of the ovaries revealed a significant age-related decrease in the mean number of primordial follicles despite DHEA supplementation. Moreover, AMH concentrations within the ovaries and circulation, assessed by Western analysis and ELISA respectively, showed significant age-related decreases that were not attenuated by DHEA supplementation. Taken together, these results fail to show a clear effect of short-term physiological DHEA supplementation on the perimenopausal ovary. However, they do not exclude the possibility that alternative DHEA supplementation paradigms (e.g., involving an earlier start date, longer duration and using pharmacological doses) may extended reproductive potential during aging.

Red cell adenosine deaminase (ADA-RBC) activity in patients with myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria is significantly increased compared to that observed in normal controls. ADA-RBC activity is not related to fetal hemoglobin concentration, but it is significantly correlated with hemoglobin concentration at diagnosis and with the degree of morphologic dysplasia in the erythroid lineage. The results of our study suggest that the observed enzymatic abnormality may constitute a non-specific manifestation of the stem cell alteration that determines these disorders.