Publications (19)63.32 Total impact
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Article: A neural network approach to evaluate fold recognition results.
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ABSTRACT: Fold recognition techniques assist the exploration of protein structures, and web-based servers are part of the standard set of tools used in the analysis of biochemical problems. Despite their success, current methods are only able to predict the correct fold in a relatively small number of cases. We propose an approach that improves the selection of correct folds from among the results of two methods implemented as web servers (SAMT99 and 3DPSSM). Our approach is based on the training of a system of neural networks with models generated by the servers and a set of associated characteristics such as the quality of the sequence-structure alignment, distribution of sequence features (sequence-conserved positions and apolar residues), and compactness of the resulting models. Our results show that it is possible to detect adequate folds to model 80% of the sequences with a high level of confidence. The improvements achieved by taking into account sequence characteristics open the door to future improvements by directly including such factors in the step of model generation. This approach has been implemented as an automatic system LIBELLULA, available as a public web server at http://www.pdg.cnb.uam.es/servers/libellula.html.Proteins Structure Function and Bioinformatics 04/2003; 50(4):600-8. · 3.39 Impact Factor -
Article: EVA: continuous automatic evaluation of protein structure prediction servers.
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ABSTRACT: Evaluation of protein structure prediction methods is difficult and time-consuming. Here, we describe EVA, a web server for assessing protein structure prediction methods, in an automated, continuous and large-scale fashion. Currently, EVA evaluates the performance of a variety of prediction methods available through the internet. Every week, the sequences of the latest experimentally determined protein structures are sent to prediction servers, results are collected, performance is evaluated, and a summary is published on the web. EVA has so far collected data for more than 3000 protein chains. These results may provide valuable insight to both developers and users of prediction methods. AVAILABILITY: http://cubic.bioc.columbia.edu/eva. CONTACT: eva@cubic.bioc.columbia.eduBioinformatics 01/2002; 17(12):1242-3. · 5.47 Impact Factor -
Article: Threading structural model of the manganese-stabilizing protein PsbO reveals presence of two possible beta-sandwich domains.
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ABSTRACT: The manganese-stabilizing protein (PsbO) is an essential component of photosystem II (PSII) and is present in all oxyphotosynthetic organisms. PsbO allows correct water splitting and oxygen evolution by stabilizing the reactions driven by the manganese cluster. Despite its important role, its structure and detailed functional mechanism are still unknown. In this article we propose a structural model based on fold recognition and molecular modeling. This model has additional support from a study of the distribution of characteristics of the PsbO sequence family, such as the distribution of conserved, apolar, tree-determinants, and correlated positions. Our threading results consistently showed PsbO as an all-beta (beta) protein, with two homologous beta domains of approximately 120 amino acids linked by a flexible Proline-Glycine-Glycine (PGG) motif. These features are compatible with a general elongated and flexible architecture, in which the two domains form a sandwich-type structure with Greek key topology. The first domain is predicted to include 8 to 9 beta-strands, the second domain 6 to 7 beta-strands. An Ig-like beta-sandwich structure was selected as a template to build the 3-D model. The second domain has, between the strands, long-loops rich in Pro and Gly that are difficult to model. One of these long loops includes a highly conserved region (between P148 and P174) and a short alpha-helix (between E181 and N188)). These regions are characteristic parts of PsbO and show that the second domain is not so similar to the template. Overall, the model was able to account for much of the experimental data reported by several authors, and it would allow the detection of key residues and regions that are proposed in this article as essential for the structure and function of PsbO.Proteins Structure Function and Bioinformatics 01/2002; 45(4):372-81. · 3.39 Impact Factor -
Article: Similarity of phylogenetic trees as indicator of protein-protein interaction.
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ABSTRACT: Deciphering the network of protein interactions that underlines cellular operations has become one of the main tasks of proteomics and computational biology. Recently, a set of bioinformatics approaches has emerged for the prediction of possible interactions by combining sequence and genomic information. Even though the initial results are very promising, the current methods are still far from perfect. We propose here a new way of discovering possible protein-protein interactions based on the comparison of the evolutionary distances between the sequences of the associated protein families, an idea based on previous observations of correspondence between the phylogenetic trees of associated proteins in systems such as ligands and receptors. Here, we extend the approach to different test sets, including the statistical evaluation of their capacity to predict protein interactions. To demonstrate the possibilities of the system to perform large-scale predictions of interactions, we present the application to a collection of more than 67 000 pairs of E.coli proteins, of which 2742 are predicted to correspond to interacting proteins.Protein engineering 10/2001; 14(9):609-14. -
Article: CAFASP2: the second critical assessment of fully automated structure prediction methods.
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ABSTRACT: The results of the second Critical Assessment of Fully Automated Structure Prediction (CAFASP2) are presented. The goals of CAFASP are to (i) assess the performance of fully automatic web servers for structure prediction, by using the same blind prediction targets as those used at CASP4, (ii) inform the community of users about the capabilities of the servers, (iii) allow human groups participating in CASP to use and analyze the results of the servers while preparing their nonautomated predictions for CASP, and (iv) compare the performance of the automated servers to that of the human-expert groups of CASP. More than 30 servers from around the world participated in CAFASP2, covering all categories of structure prediction. The category with the largest participation was fold recognition, where 24 CAFASP servers filed predictions along with 103 other CASP human groups. The CAFASP evaluation indicated that it is difficult to establish an exact ranking of the servers because the number of prediction targets was relatively small and the differences among many servers were also small. However, roughly a group of five "best" fold recognition servers could be identified. The CASP evaluation identified the same group of top servers albeit with a slightly different relative order. Both evaluations ranked a semiautomated method named CAFASP-CONSENSUS, that filed predictions using the CAFASP results of the servers, above any of the individual servers. Although the predictions of the CAFASP servers were available to human CASP predictors before the CASP submission deadline, the CASP assessment identified only 11 human groups that performed better than the best server. Furthermore, about one fourth of the top 30 performing groups corresponded to automated servers. At least half of the top 11 groups corresponded to human groups that also had a server in CAFASP or to human groups that used the CAFASP results to prepare their predictions. In particular, the CAFASP-CONSENSUS group was ranked 7. This shows that the automated predictions of the servers can be very helpful to human predictors. We conclude that as servers continue to improve, they will become increasingly important in any prediction process, especially when dealing with genome-scale prediction tasks. We expect that in the near future, the performance difference between humans and machines will continue to narrow and that fully automated structure prediction will become an effective companion and complement to experimental structural genomics.Proteins Structure Function and Bioinformatics 02/2001; Suppl 5:171-83. · 3.39 Impact Factor -
Article: Mechanisms of reduced body growth in the pubertal feminized male rat: unbalanced estrogen and androgen action on the somatotropic axis.
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ABSTRACT: It is well known that the sex difference in body growth at puberty is modulated by a complex interplay between sex steroids and somatotropic axis; however, the exact role played by sex steroids remains a matter of controversy. The aim of this study was to assess the mechanisms by which sex steroids regulate body growth during pubertal development. Flutamide, a non-steroid-blocking androgen receptor, was subcutaneously administered to 30-d-old male Wistar rats for 4 wk. The blockade of the androgen receptor led to a marked elevation in serum testosterone and an increment in serum estradiol. Flutamide administration decreased body weight gain, serum IGF-I levels, hepatic IGF-I mRNA, and GH receptor mRNA content. There were no significant changes in serum GH concentration, pituitary GH reserve, and pituitary GH mRNA content. Flutamide lowered hypothalamic somatostatin mRNA content and augmented hypothalamic immunoreactive somatostatin stores, but did not alter hypothalamic immunoreactive GH-releasing factor stores. Our findings indicate that during pubertal development of the male rat, the imbalance between androgen and estrogen actions determines an abnormal somatic growth, which is at least partly exerted through the peripheral or hepatic modification of the somatotropic axis that occurs under the high or exclusive action of estrogens. Potential implication of coincident sex-specific regulated mode of pulsatile GH secretion cannot be excluded from this random serum GH sample study.Pediatric Research 08/2000; 48(1):96-103. · 2.70 Impact Factor -
Article: A platform for integrating threading results with protein family analyses.
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ABSTRACT: We have developed a package for the interactive visualization of results from different threading programs. Additionally, we have integrated relevant information about protein sequence, function, evolution, and structure into the interface.Bioinformatics 01/2000; 15(12):1062-3. · 5.47 Impact Factor -
Article: Regulation of gonadal and somatotropic axis by chronic intraventricular infusion of insulin-like growth factor 1 antibody at the initiation of puberty in male rats.
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ABSTRACT: There has been increasing experimental evidence to suggest that insulin-like growth factor 1 (IGF-I) may be one of the essential regulators in the reproductive system of the rat. IGF-I is synthesized in the hypothalamus and IGF-I immunoreactivity increases during puberty. Consequently we hypothesized that centrally located IGF-I might contribute to the initiation of puberty. Centrally located IGF-I was immunoneutralized to assess this hypothesis. Male Wistar rats, 28 days old, were infused intracerebroventricularly with specific purified IgGs from rabbit IGF-I antiserum (IGF-I-Ab). The intracerebroventricular administration of IGF-I-Ab resulted in a reduction in testicular weight and consequently in delayed pubertal development. There was also a reduction in serum testosterone, pituitary immunoreactive (IR) luteinizing hormone (LH) and serum IR follicle-stimulating hormone (FSH). The accumulation of betaLH mRNA was not modified, whereas betaFSH mRNA was increased. An increment in the serum growth hormone (GH) levels was also observed. There were no significant alterations in hypothalamic IR growth hormone releasing factor content, although IR somatostatin (SRIH) content was increased by IGF-I-Ab. The body weight gain remained unaltered. As a whole, our study suggests that centrally located IGF-I influences pubertal development, production and release of gonadotropins and supports the finding that endogenous centrally located IGF-I plays a role at the initiation of puberty in the male rat. It also gives support to the physiological role of centrally located IGF-I in the release of GH mediated by hypothalamic SRIH at the initiation of puberty.Neuroendocrinology 07/1999; 69(6):408-16. · 2.38 Impact Factor -
Article: Prospective randomized study comparing the long-acting gonadotropin-releasing hormone agonist triptorelin, flutamide, and cyproterone acetate, used in combination with an oral contraceptive, in the treatment of hirsutism.
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ABSTRACT: To compare triptorelin, cyproterone acetate (CPA), and flutamide, in combination with an oral contraceptive, in the treatment of hirsutism. Prospective randomized study. Tertiary care hospital. Thirty-nine hirsute women with idiopathic or functional ovarian hyperandrogenism. Patients were randomly assigned to receive triptorelin (3.75 mg IM every 28 days), CPA (100 mg/d orally on days 1-10 of the menstrual cycle), or flutamide (250 mg orally twice daily). All the patients also received a triphasic oral contraceptive. Before and after 3 and 9 months of treatment, the Ferriman-Gallwey score, hepatic function, and gonadal and adrenal steroid profiles were evaluated. Thirty-three patients completed the 9-month study period. The Ferriman-Gallwey score decreased in all the groups. In the patients treated with CPA or flutamide, a decrease in the hirsutism score was noted as soon as after 3 months of treatment. This decrease was more pronounced after 9 months of treatment, especially in the patients who received flutamide, who had lower hirsutism scores compared with the other treatment groups. None of the patients had abnormal liver function test results. There was a mild increase in serum lipid concentrations, mostly in the group treated with triptorelin. Triptorelin, CPA, and flutamide are effective drugs for the treatment of hirsutism. Flutamide results in a greater reduction in the hirsutism score, but CPA also offers satisfactory results at a much lower cost. Triptorelin has no advantages over flutamide and CPA, and is the most expensive of the three drugs tested.Fertility and Sterility 02/1999; 71(1):122-8. · 3.56 Impact Factor -
Article: Direct action of serotonin on prolactin, growth hormone, corticotropin and luteinizing hormone release in cocultures of anterior and posterior pituitary lobes: autocrine and/or paracrine action of vasoactive intestinal peptide.
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ABSTRACT: There is extensive evidence that serotonin (5-HT) is implicated in the neuroendocrine control regulating the secretion of several anterior pituitary hormones. It has also been reported that the posterior pituitary is necessary for prolactin (PRL) response to 5-HT as well as to suckling, in which 5-HT implication has been demonstrated. As we have previously shown that vasoactive intestinal peptide (VIP) mediates through an autocrine or paracrine action the PRL release induced by insulin-like growth factor I, thyrotropin-releasing hormone (TRH) and dopamine withdrawal, the aim of the present work was to determine whether 5-HT has a direct action on pituitary secretion and to study the possible role of pituitary VIP in this situation. Cells from the anterior pituitary lobe (AP) were cultured either alone or together with cells from the posterior pituitary lobe (PP). As melanotropes from PP express glucocorticoid receptors in vitro, both AP cultures and cocultures of AP/PP cells were incubated in the presence or absence of corticosterone (0.1 microg/ml), thus designing four experimental conditions. Then both AP and mixed cultures were incubated with 5-HT (100 nM) for 20, 45 and 180. The release of PRL, growth hormone (GH), corticotropin (ACTH) and luteinizing hormone (LH) was stimulated by 5-HT, but only in cocultures of AP/PP cells preincubated with corticosterone, whereas follicle-stimulating hormone and thyroid-stimulating hormone release was not modified. As AP cultures did not show any response to 5-HT, both in the presence or absence of corticosterone, and as melanotropes are the main cellular type present in the PP cultures, we studied the response of alpha-melanocyte-stimulating hormone (alphaMSH) to 5-HT in PP cells cultured with or without corticosterone. Serotonin did not modify alphaMSH release either in the absence or the presence of corticosterone. VIP release was also stimulated by 5-HT in the cocultures, and the time response profile was only similar to that of PRL. In order to study whether pituitary VIP is implicated in 5-HT action, cocultures preincubated with corticosterone were incubated in the presence of 5-HT, a VIP-receptor antagonist (VIP-At) or simultaneously with 5-HT plus VIP-At. PRL response to 5-HT was abolished by the simultaneous presence of VIP-At, whereas GH, ACTH and LH response remained unchanged. These data demostrate that: (1) 5-HT stimulates the secretion of PRL, GH, ACTH, LH and VIP acting directly at pituitary level on PP, probably by releasing an unidentified mediator from melanotropes; (2) glucocorticoids make the response of AP cells to 5-HT possible due to the presence of PP cells in the coculture; (3) PRL response to 5-HT is mediated through an autocrine and/or paracrine action of VIP.Neuroendocrinology 12/1998; 68(5):326-33. · 2.38 Impact Factor -
Article: Hormonal studies in Cushing's syndrome during petrosal sinus catheterization. Part II: Absence of relationship between intestinal vasoactive peptide and prolactin.
Hormone and Metabolic Research 09/1997; 29(8):409-10. · 2.19 Impact Factor -
Article: Correlated mutations contain information about protein-protein interaction.
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ABSTRACT: Many proteins have evolved to form specific molecular complexes and the specificity of this interaction is essential for their function. The network of the necessary inter-residue contacts must consequently constrain the protein sequences to some extent. In other words, the sequence of an interacting protein must reflect the consequence of this process of adaptation. It is reasonable to assume that the sequence changes accumulated during the evolution of one of the interacting proteins must be compensated by changes in the other. Here we apply a method for detecting correlated changes in multiple sequence alignments to a set of interacting protein domains and show that positions where changes occur in a correlated fashion in the two interacting molecules tend to be close to the protein-protein interfaces. This leads to the possibility of developing a method for predicting contacting pairs of residues from the sequence alone. Such a method would not need the knowledge of the structure of the interacting proteins, and hence would be both radically different and more widely applicable than traditional docking methods. We indeed demonstrate here that the information about correlated sequence changes is sufficient to single out the right inter-domain docking solution amongst many wrong alternatives of two-domain proteins. The same approach is also used here in one case (haemoglobin) where we attempt to predict the interface of two different proteins rather than two protein domains. Finally, we report here a prediction about the inter-domain contact regions of the heat- shock protein Hsc70 based only on sequence information.Journal of Molecular Biology 09/1997; 271(4):511-23. · 4.00 Impact Factor -
Article: A graphical interface for correlated mutations and other protein structure prediction methods.
Computer applications in the biosciences: CABIOS 07/1997; 13(3):319-21. -
Article: Growth hormone induces somatostatin and insulin-like growth factor I gene expression in the cerebral hemispheres of aging rats.
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ABSTRACT: The neuropeptide somatostatin (SS) plays a role as a modulator of cognitive functions and as a potential tropic factor in the central nervous system. A reduction in SS levels has been demonstrated in the aging brain and in dementia. In addition, insulin-like growth factor I (IGF-I) acts as a paracrine factor in multiple GH actions and is also found in the cerebral hemispheres, where it exerts neurotropic effects. We used aging rats as an in vivo model of GH deficiency to study the possible participation of exogenous GH in the modulation of the cerebral hemispheric SS and IGF-I. Two sets of experiments were carried out. In the first set, the age-related patterns of GH, IGF-I, and SS in the serum, pituitary, and cerebral hemispheres were established. In the second experimental set, 90-day-old (adult) and 2-yr-old (aging) male rats received recombinant human GH (200 micrograms/ sc-day) or vehicle for 7 consecutive days. The serum levels of rat GH and IGF-I as well as pituitary GH messenger RNA decreased in 2-yr-old rats compared with those in adult rats. After GH treatment, pituitary GH messenger RNA levels decreased markedly in the 90-day-old and 2-yr-old rats. Serum immunoreactive GH decreased in the adult animals, whereas it remained unaffected in the aging ones, whereas serum IGF-I levels were not altered by GH treatment in either group. Immunoreactive levels and messenger RNA of both SS and IGF-I were low in the cerebral hemispheres of aging rats, but were restored to the levels found in adult rats after GH treatment. As treatment did not induce changes in the serum IGF-I levels, these results provide evidence of a stimulatory action of peripherally administered GH on the regulation of SS and IGF-I genes in the aging rat in the central nervous system. These data also show a new target action for GH and could provide a molecular basis for the improvement of some symptoms of GH deficiency that occurs after recombinant human GH treatment.Endocrinology 11/1996; 137(10):4384-91. · 4.46 Impact Factor -
Article: Autoparacrine action of vasoactive intestinal peptide on dopaminergic control of prolactin secretion.
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ABSTRACT: We have previously reported that pituitary vasoactive intestinal peptide (VIP) mediates through autoparacrine mechanisms insulin-like growth factor-I and TRH-stimulated PRL release. In the present study, we have investigated whether VIP might also be implicated in the PRL increase that follows dopamine (DA) withdrawal. The experiments were carried out in defined medium supplemented or not with T3, as in a previous study we had found that PRL release increases under low T3 culture conditions due to mediation by concomittant stimulus of VIP. Anterior pituitary (AP) cells from adult male rats were incubated for 1 h in the presence of DA (10 microM), a VIP-receptor antagonist (VIP-At) (200 nM), or DA plus VIP-At. Then media were removed and the cells were washed with PBS and reincubated under the same conditions but without the addition of DA. In the first incubation, DA inhibited PRL release by 80%, and VIP release by 20% in both T3-free and T3 medium. In the second period of incubation, PRL and VIP release were increased in AP cells previously exposed to DA. These effects were greater when the cells were cultured in T3-free medium than in T3-medium (225% and 150%, respectively for PRL release; and 155 and 135%, respectively for VIP release). PRL response to DA withdrawal was inhibited by the simultaneous presence of VIP-At. This inhibition was again greater when the cells were incubated in medium supplemented with T2. Thus, the stimulus of DA withdrawal was inhibited by 88% in T2-free medium and by 37% in T3-medium. To investigate whether pituitary VIP messenger RNA (mRNA) expression is under dopaminergic control, AP cells were incubated in the presence or absence of bromocriptine (BC) (10 nM) for 2 and 24 h. After 24 h of incubation, BC decreased mRNA levels of PRL and of the two transcripts which VIP expresses in AP. As with DA, BC also inhibited PRL and VIP release both at 2 and 24 h. These data demonstrate that VIP, at least partially, mediates DA withdrawal-induced PRL release through an autoparacrine action. They also suggest that simultaneous inhibition of pituitary VIP mRNA expression and VIP release may be a necessary mechanism for the dopaminergic inhibition of PRL mRNA expression and PRL release.Endocrinology 03/1996; 137(2):508-13. · 4.46 Impact Factor -
Article: Autocrine and/or paracrine action of vasoactive intestinal peptide on thyrotropin-releasing hormone induced prolactin release.
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ABSTRACT: Several in vitro studies have demonstrated that vasoactive intestinal peptide (VIP) modulates basal PRL release in normal and hypothyroid anterior pituitary (AP) cells through an autocrine or paracrine action. As thyroid hormone is an important factor in the regulation of pituitary VIP synthesis and secretion, we analyzed the influence of the absence of thyroid hormone on basal PRL release in vitro to study whether the release of PRL induced by TRH might be mediated by a local action of pituitary VIP. When normal AP cells were cultured in a medium supplemented with a near-physiological concentration of free T2 (0.5 nM), basal PRL and VIP release decreased and PRL secretion was not altered by the blockade of VIP action. This finding allowed us to establish the culture conditions in which basal PRL secretion is apparently not under VIP influence. Consequently, we were able to study whether pituitary VIP may be implicated in TRH-induced PRL release. TRH (100 nM) increased PRL and VIP release in a parallel manner and decreased PRL and VIP intracellular content in incubations from 15-180 min. When AP cells wee incubated simultaneously with TRH and a VIP receptor antagonist, TRH-induced PRL release decreased when incubation lasted more than 30 min, whereas the depletion of PRL intracellular content induced by TRH was unchanged. TRH also slightly increased VIP messenger RNA levels at 3 and 24 h, but PRL messenger RNA levels were not modified. These data demonstrate that pituitary VIP participates in in TRH-induced PRL release and that the effect of thyroid hormone on basal pituitary VIP secretion should be borne in mind when studies on its effect, through autocrine and/or paracrine mechanisms, on PRL release stimulated by PRL-releasing factors are conducted.Endocrinology 02/1996; 137(1):144-50. · 4.46 Impact Factor -
Article: Long-term thyroid replacement therapy and levels of lipoprotein(a) and other lipoproteins.
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ABSTRACT: There is a general interest to know whether lipoprotein(a) [Lp(a)] is under hormonal control. Hypothyroidism is a well known cause of secondary hyperlipidemia, which mainly affects low density lipoprotein (LDL) cholesterol levels, but the result on the effects of L-T4 replacement therapy on the Lp(a) concentration is controversial. We studied 12 severely hypothyroid, hypercholesterolemic patients under basal conditions and during L-T4 treatment. We found a rapid decrease in both LDL cholesterol (5.71 +/- 0.62 vs. 4.37 +/- 0.44 mmol/L basally and after 1 month of thyroid replacement, respectively) and apolipoprotein-B (Apo-B) levels (1.89 +/- 0.02 vs. 1.52 +/- 0.17 g/L, respectively); these changes persisted for up 1 yr of analytical euthyroidism and paralleled the improvement in the thyroid status of the patients. In contrast, the plasma Lp(a) concentration did not change at any time (496 +/- 123, 464 +/- 128, and 441 +/- 110 mg/L under basal conditions and after 1 and 14-15 months of thyroid replacement, respectively), and the small fluctuations observed in some patients did not correlate with those in LDL cholesterol or Apo-B, and were not associated with any particular Apo(a) phenotype. In relation to HDL fractions, high density lipoprotein3 (HDL3) remained stable, but HDL2 cholesterol and phospholipid levels decreased during treatment, changes that were the inverse of those in postheparin plasma hepatic lipase activity. Patients in the present study were normotriglyceridemic, except one who was hypertriglyceridemic at diagnosis, but even in this patient, triglyceride levels were unaffected by T4 substitution therapy, as was postheparin plasma lipoprotein lipase activity. The changes observed in LDL, HDL2, and hepatic lipase activity delineate the lipoprotein-related response to T4 replacement therapy, whereas potential individual fluctuations in Lp(a) levels are probably more dependent on other factors, such as the production rate, which are not affected by thyroid hormones.Journal of Clinical Endocrinology & Metabolism 03/1995; 80(2):562-6. · 6.50 Impact Factor -
Article: Ovarian suppression with triptorelin and adrenal stimulation with adrenocorticotropin in functional hyperadrogenism: role of adrenal and ovarian cytochrome P450c17 alpha.
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ABSTRACT: To validate combined ovarian suppression with triptorelin and adrenal stimulation with ACTH in the diagnosis of female hyperandrogenism and to provide new insights into the adrenal-ovarian relationship present in this disorder. Comparison of sexual steroids and basal and ACTH-stimulated steroid levels before and after ovarian suppression induced by triptorelin. Department of Endocrinology, Hospital Ramón y Cajal, Madrid, Spain. Thirty-nine nonselected women with hyperandrogenism. Serum levels of T, 17-hydroxyprogesterone (17-OHP), 17-hydroxy-pregnenolone, DHEA and DHEAS, androstenedione (delta 4-A), 11-deoxycortisol, and cortisol. Elevated T independent of ovarian suppression pointed to an adrenal disorder in six patients (one with an androgen-producing adenoma, two with late-onset 21-hydroxylase deficiency, three with functional adrenal hyperandrogenism). Nineteen patients had functional ovarian hyperandrogenism as elevated T normalized after ovarian suppression and were subdivided into ovDHEAS+ (n = 7) and ovDHEAS = (n = 12) subgroups depending on the presence of DHEAS hypersecretion. Finally, 14 patients had idiopathic hirsutism according to normal T before and after ovarian suppression. Comparisons of initial hormonal values between groups and with reference values obtained from normal women (n = 11) disclosed in functional adrenal hyperandrogenism an elevation of T and basal and stimulated DHEAS, delta 4-A, and 17-OHP with respect to normal women. These abnormalities were also present in ovDHEAS+ except for basal delta 4-A, which was normal, whereas only T and stimulated 17-OHP were elevated in ovDHEAS =. In the idiopathic group all steroids were normal with the exception of a mild elevation in stimulated DHEAS. These results show a continuum of abnormalities in hyperandrogenic women, suggesting an enhanced cytochrome P450c17 alpha activity in the adrenal and the ovary as the shared mechanism between functional adrenal hyperandrogenism and functional ovarian hyperandrogenism.Fertility and Sterility 10/1994; 62(3):521-30. · 3.56 Impact Factor -
Article: Differential regulation of gonadotropins and glycoprotein hormone alpha-subunit by IGF-I in anterior pituitary cells from male rats.
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ABSTRACT: IGF-I has been demonstrated to stimulate basal and GnRH-induced gonadotropin release. IGF-I also elicites alpha-subunit secretion in human pituitary tumor cells. The aims of this study were to evaluate both the effect of IGF-I on gonadotropin LH-beta and FSH-beta mRNA levels and glycoprotein alpha-subunit gene expression in cultured rat anterior pituitary cells. The exposure of pituitary cells to recombinant human IGF-I (rhlGF-I; 2 microg/ml) for 72 h markedly stimulated basal LH and FSH release whereas their mRNA levels remained unmodified. IGF-I elicited a-subunit release from pituitary cells (p < 0.01) and augmented its mRNA levels. Exposure to IGF-I consistently reduced GH release from pituitary cells. This study shows that the gonadotropin-releasing effects of IGF-I are not paralleled by changes in their mRNAs whereas IGF-I stimulates not only alpha-subunit release but also its mRNA levels. This study provides the first observation of alpha-subunit regulation by IGF-I in normal pituitary cells, where a differential regulation between release and synthesis for gonadotropin a-and 1-subunits is also shown.Journal of endocrinological investigation 27(7):670-5. · 1.57 Impact Factor
Top co-authors
Top Journals
Institutions
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2002–2003
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Centro Nacional de Biotecnología (CNB)
Madrid, Madrid, Spain
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1994–2000
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Hospital Universitario Ramón y Cajal
Madrid, Madrid, Spain
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1996
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Instituto de Salud Carlos III
Madrid, Madrid, Spain
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