Valeria Valentino

Plasma brain-derived neurotrophic factor daily variations in men: correlation with cortisol circadian rhythm

Expression and secretion of neurotrophins, including brain-derived neurotrophic factor (BDNF), are regulated also by neuronal activity. Data available in the literature suggest that BDNF central levels are influenced by light and dark. Diurnal changes of BDNF mRNA and protein contents have been demonstrated in the rat central nervous system. Based on these pieces of evidence, we investigated the hypothesis of a possible diurnal variation of BDNF circulating levels in human males. Moreover, we looked for a possible correlation with cortisol circadian rhythm, since both BDNF and cortisol are implicated in the maintenance of cerebral functions. In this study, 34 healthy young male volunteers were included. Five blood samples were drawn from each subject thrice in a month at regular 4-h intervals (0800, 1200, 1600, 2000, and 2400 h). BDNF and cortisol were measured in all samples. BDNF was determined by ELISA method. Our results show that plasma BDNF levels, as well as cortisol levels, are significantly higher in the morning when compared with the night (P<0.001), with a trend of constant decrease during the day. Furthermore, plasma BDNF and cortisol are positively correlated (Spearman index=0.8466). The present study is the first to demonstrate the presence of a diurnal rhythm of BDNF in humans. Moreover, the correlation found out between BDNF and cortisol circadian trend allows us to speculate that these two factors may be physiologically co-regulated, in order to maintain the homeostasis of integrated cerebral activities.

Brain-derived neurotrophic factor plasma variation during the different phases of the menstrual cycle in women with premenstrual syndrome

Premenstrual syndrome (PMS) is characterized by a cluster of psychological and somatic symptoms that begin during the late luteal phase of the menstrual cycle and disappear after the onset of menses. Since PMS might be caused by an alteration in the cyclical hormonal modifications and ovarian steroids are directly involved in the regulation of mood, affective and cognitive functions and influence neurotrophins expression, in particular the brain-derived neurotrophic factor (BDNF), we aimed to evaluate whether plasma BDNF levels in women with PMS differ from those of normally menstruating women without PMS. Sixty-two women were divided into two groups: one group of women (n=35) with PMS and one group (n=27) composed by normally menstruating women. Plasma samples were collected at day 7 (follicular phase) and day 21 (luteal phase) of the menstrual cycle. Plasma BDNF of the control group significantly increased (p<0.001) from the follicular phase (402.90±74.41pg/ml) to the luteal phase (1098.79±146.49pg/ml). On the other hand, in the PMS group plasma BDNF levels significantly decreased (p<0.001) from the follicular phase (412.45±78.35pg/ml) to the luteal phase (233.03±75.46pg/ml) Luteal BDNF levels of the PMS women were significantly lower than those of the control group (p<0.001). In women with PMS, plasma BDNF followed a decreasing trend during the ovarian cycle, in opposition to the increasing trend observed in women without PMS. The lower luteal BDNF levels of the PMS women might be a consequence of an altered hormonal response and might play a role in the onset of the symptoms PMS related.

Vascular endothelial growth factor and basic fibroblast growth factor in polycystic ovary syndrome during controlled ovarian hyperstimulation

Background. Polycystic ovary syndrome (PCOS) is a common endocrine disorder that causes anovulation and consequent subfertility. It is well established that increased ovarian mass, supported by new blood vessel proliferation in stroma and theca, is a key feature of PCOS. Recent studies suggest a role for angiogenetic factors in this phenomenon. Aim. To evaluate of levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in serum and follicular fluid of PCOS patients during a controlled ovarian hyperstimulation. Methods. In 52 patients undergoing in vitro fertilization treatments, 26 PCOS patients and 26 controls, serum VEGF and bFGF levels were assessed before starting administration of follicle-stimulating hormone (FSH) (day 0), on the day of administration of human chorionic gonadotropin (hCG) and on the day of oocyte retrieval. Follicular fluid levels of the two growth factors were detected on the day of oocyte retrieval. Results. PCOS patients showed higher serum VEGF levels than controls before starting FSH administration, on the day of hCG administration and on the day of oocyte retrieval. Serum VEGF levels showed a rise after hCG administration only in the PCOS patients. In addition, serum bFGF levels were higher in PCOS patients than in controls on the day of hCG administration and the day of oocyte retrieval. Furthermore, on the day of hCG administration, serum bFGF levels were directly correlated to the amount of FSH previously administered (p < 0.0001). In follicular fluid, higher VEGF and bFGF levels were found in PCOS patients than in controls. Furthermore, follicular-fluid bFGF concentrations were inversely correlated with the percentage of mature oocytes collected (p < 0.05). Conclusions. The present study revealed elevated levels of VEGF and bFGF in serum and follicular fluid in PCOS patients compared with controls. bFGF seems to be an FSH-dependent growth factor and its levels in follicular fluid are inversely correlated with the percentage of mature oocytes collected.

One-year therapy with 10 mg/day DHEA alone or in combination with HRT in postmenopausal women: Effects on hormonal milieu

The purpose of this study was to evaluate the effects on hormonal milieu of 1-year therapy with 10 mg/day oral dehydroepiandrosterone (DHEA) or 50 microg transdermal estradiol plus 100 mg/day oral micronized progesterone in a group of 20 healthy postmenopausal women (age=50-58 and years since menopause (ysm)=1-6) and also the effects observed by combining these two therapies in a group of 12 postmenopausal women (age=54-61 and ysm=6-10) characterized by lower baseline DHEA and DHEAS levels (<2.40 and <0.55 microg/ml, respectively). DHEA produced a significant rise in androgens levels, whereas HRT did not. Moreover, DHEA alone induced a significantly lower increase in estrogens and beta-endorphin levels and a higher decrease in cortisol levels than HRT. DHEA and HRT also produced a significant similar increase in allopregnanolone levels. DHEA plus HRT induced a significantly higher increase in testosterone and estradiol and a lower increase in allopregnanolone and beta-endorphin levels and a significantly lower decrease in cortisol levels than HRT alone treated group. A similar increase was observed in progesterone and SHBG levels in all groups. These results suggest that 10-mg DHEA seems to be the proper dose to replace androgen deficiency in subjects with reduced Delta-5 androgens plasma levels. However, the aging process and the number of years since menopause may further modulate the effects of hormone therapy on hormonal milieu.

Effects of nomegestrol acetate administration on central and peripheral beta-endorphin and allopregnanolone in ovx rats

The aim of this study was to investigate the effects of nomegestrol acetate (NOMAc) on the central nervous system by analyzing the neurosteroid allopregnanolone and the opioid beta-endorphin (beta-endorphin). 104 Wistar female rats were used in this study; one group of fertile and one group of ovariectomized rats were used as control. The others were ovariectomized and they underwent a 2-week oral treatment of NOMAc (0.05, 0.1, 0.2, 0.5, 1mg/kg/day), alone or with 0.05 mg/kg/day of estradiol valerate (E2V). Allopregnanolone and beta-endorphin were assessed in different brain areas and in circulation. Ovariectomy decreased allopregnanolone anywhere except in the adrenal gland and E2V reversed the effects of ovariectomy. 0.5 and 1mg/kg/day of NOMAc increased allopregnanolone levels in hippocampus. Combined administration of 1mg/kg/day of NOMAc plus E2V induced a further increase of allopregnanolone levels in hippocampus, hypothalamus, and anterior pituitary. NOMAc (1mg/kg/day) decreased the adrenal content of allopregnanolone, both by itself and associated with E2V. NOMAc increased hippocampal and hypothalamic content of beta-endorphin at the highest doses, and it increased positively E2V action, at 1mg/kg/day, also in anterior pituitary and plasma. These findings reinforce the clinical data regarding the capability of NOMAc to modulate the pathways involved in mood and behaviour. In fact, due to the NOMAc action on hippocampus, hypothalamus, and anterior pituitary, our results highlight the selectivity of NOMAc on part of the limbic system and the anterior pituitary, regarding both allopregnanolone and beta-endorphin.

Vascular endothelial growth factor level changes during human embryo development in culture medium.

Objective. Implantation is a complex phenomenon consisting of the first strong contact between embryo and endometrium. Recent studies have demonstrated that this process is dependent not only on the ‘readiness’ of the endometrium, but also on complex interactions between endometrial and embryonic tissues that cross-talk by means of different molecules (growth factors, cytokines, vasoactive factors). Investigations performed on human blastocysts indicate a role for vascular endothelial growth factor (VEGF) in these processes. The aim of the present study was to investigate VEGF levels at different stages in human embryo culture medium. Study design. We selected 20 women among patients undergoing assisted reproduction with the in vitro fertilization–blastocyst transfer protocol. The oocytes were inseminated by intracytoplasmic sperm injection. For each patient, approximately two cultures of four microinjected oocytes (and then of four embryos) were performed. Each culture of four oocytes/embryos was placed in one dish to increase the probability to detect small VEGF concentrations. Results. Results showed significantly higher VEGF levels in the medium at blastocyst stage (12.16 ± 2.80 pg/ml) compared with embryos at pronuclear stage (13.58 ± 2.32 pg/ml) and microinjected oocytes (12.80 ± 3.45 pg/ml). Conclusions. An important VEGF synthesis by blastocysts occurs during human embryo development.

Chromosomal abnormalities in women with premature ovarian failure

Premature ovarian failure is a complex disorder that results in the early loss of ovarian function; however this disease must be separated from early menopause because these patients can sporadically ovulate and in literature are described pregnancies. The aetiology and the patho-physiology of premature ovarian failure are still matter of debate, but is commonly accepted that genetic factors play an important role. This review is aimed to present an overview of known inherited factor implied in the pathogenesis of this disorder to help physician in the counselling of affected pregnant women.

Vascular endothelial growth factor in females of reproductive age

The development of a vascular supply is essential not only for organ growth and differentiation during embryogenesis, but also for wound healing and reproductive functions in adults1. Angiogenesis is usually quiescent in adults, except when required in pathological situations (such as diabetic retinopathy, rheumatoid arthritis, cardiac ischemia and tumor growth) and for highly ordered, cycle-specific, physiological processes of the female reproductive system (ovulation, menstruation, implantation and pregnancy)2. Vascular development occurs in two stages: an early stage (vasculogenesis), and a later stage (angiogenesis)3. Vasculogenesis is the mechanism by which the primary capillary network is formed from mesoderm-derived precursors (hemangioblasts), through a process of differentiation, proliferation, and coalescence to form the primitive vascular network4,5. Angiogenesis is the formation of new capillary blood vessels from pre-existing microvessels by remodeling of the primary plexus. This process is regulated through a balance of soluble angiogenic stimulatory and inhibitory factors6,7. Disturbance of this balance may result in a disrupted physiological state in various pathological conditions. Over the past decade, some authors have searched for potential regulators of angiogenesis, and they have found numerous candidates: acid fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), transforming growth factor-α (TGFα), transforming growth factor-β (TGFβ), hepatocyte growth factor, tumor necrosis factor-α (TNFα), angiogenin and interleukin-8 (IL-8)8,9. Also, extensive research10–16 has been carried out on members of the vascular endothelial growth factor (VEGF) gene family. There is strong evidence that this family plays a fundamental role in the angiogenetic process as well as in vascular permeability. VEGF is a basic heparin-binding, homodimeric glycoprotein of 45 kD, which binds specifically to receptors on endothelial cells. The human VEGF gene has been localized to chromosome 6p21.3, composed of eight exons separated by seven introns. VEGF exists in five isoforms resulting from alternative splicing of the same gene, and acts through tysrosine kinase family receptors17. The five isoform are: VEGF-A, VEGF-B, VEGF-C, VEGF-D and placental growth factor (PLGF). Five VEGF forms have been identified in mammals, resulting from alternative splicing of the single VEGF gene: Gynecol Endocrinol 2003;17:477–492

Testosterone Therapy and Women‗s Sexuality

The relative contribution of androgen and oestrogen to female sexual function is controversial. Low libido, decreased wellbeing, blunted motivation and fatigue are listed as major features of the proposed syndrome of female androgen deficiency.1,2 However, defining and elucidating this syndrome has been problematic. First, the symptoms are vague and difficult to objectify, and can all occur in other syndromes such as major depressive disorders. Second, there is no consensus on the definition of low testosterone (T) levels. This lack reflects assay difficulties and insufficient studies establishing the normal range of androgen levels in different phases of life. In fact, T levels reach an apparent peak in the early reproductive years (early 20s) and decrease with age. Women in their 40s have approximately half the level of circulating total T as women in their 20s.3 The rate of the age-related decrease in total T then seems to slow, and is not specifically related to menopause. Dehydroepiandrosterone sulphate (DHEAS) shows similar changes to those described for T, but has an even more pronounced age-related decrease after the early reproductive years that continues through to later life.4

La contraccezione della prima volta e sessualità

The adolescence reference models are quickly changing in relation to the transformation of the communication. Nowadays this is the background of sexuality discovery. Sexual health needs a constant care, made by the experts, on this changings. Therefore, sexual education is the best instrument to promote the individual and the couple well-being by providing tools to get throw the contradictions between sexual approach and the knowledge about it.