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Joaquin Lado-Abeal

Publications and source records attributed to Joaquin Lado-Abeal.

9 recordsLinked to original sources
PubMed2005

Mutations in SECISBP2 result in abnormal thyroid hormone metabolism.

Incorporation of selenocysteine (Sec), through recoding of the UGA stop codon, creates a unique class of proteins. Mice lacking tRNA(Sec) die in utero, but the in vivo role of other components involved in selenoprotein synthesis is unknown, and Sec incorporation defects have not been described in humans. Deiodinases (DIOs) are selenoproteins involved in thyroid hormone metabolism. We identified three of seven siblings with clinical evidence of abnormal thyroid hormone metabolism. Their fibroblasts showed decreased DIO2 enzymatic activity not linked to the DIO2 locus. Systematic linkage analysis of genes involved in DIO2 synthesis and degradation led to the identification of an inherited Sec incorporation defect, caused by a homozygous missense mutation in SECISBP2 (also called SBP2). An unrelated child with a similar phenotype was compound heterozygous with respect to mutations in SECISBP2. Because SBP2 is epistatic to selenoprotein synthesis, these defects had a generalized effect on selenoproteins. Incomplete loss of SBP2 function probably causes the mild phenotype.

Adolescent↗
PubMed2005

Subcutaneous administration of pulsatile gonadotropin-releasing hormone decreases serum follicle-stimulating hormone and luteinizing hormone levels in women with polycystic ovary syndrome: a preliminary study.

OBJECTIVE: The main objectives of this study were to investigate whether [1] subcutaneous (SC) administration of pulsatile gonadotropin-releasing hormone (GnRH) decreases the increased levels of luteinizing hormone (LH) observed in women with polycystic ovary syndrome (PCOS); and [2] GnRH administration modifies the pattern of LH secretion observed in these patients. DESIGN: Serum follicle-stimulating hormone (FSH) and LH levels and LH pulse amplitude and pulse interval were determined in 13 patients with PCOS during the first 3 days of the cycle following the administration of 10 mg of medroxyprogesterone acetate during 5 days. SETTING: Infertility clinic. PATIENT(S): Thirteen women with PCOS. INTERVENTION(S): Determination of FSH and LH serum levels after SC administration of pulsatile GnRH. MAIN OUTCOME MEASURE(S): The FSH and LH levels in serum. RESULT(S): Mean FSH and LH levels in serum decreased following the administration of subcutaneous pulsatile GnRH in all treated women compared with baseline values. The LH pulse amplitude and pulse interval decreased in all patients following the administration of pulsatile GnRH. CONCLUSION(S): The SC administration of pulsatile GnRH in women with PCOS significantly decreases FSH and LH levels in serum. A decrease in the secretion of gonadotropins, without reaching the intense suppression observed with GnRH analogues, could be of great utility in in vitro fertilization (IVF) treatments.

Adult↗
PubMed2004

A de novo mutation in an already mutant nucleotide of the thyroid hormone receptor beta gene perpetuates resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) is a syndrome of reduced sensitivity to thyroid hormone, most commonly caused by mutations in the thyroid hormone receptor (TR) beta gene. Mutations are mostly located in the ligand-binding domain of the TRbeta, decreasing T(3) binding to the mutant TRbeta molecule, which in turn interferes with the function of the wild-type (WT) TR. A total of 122 different TRbeta gene mutations have been identified so far, with 46 occurring in more than one family. We now report a family with two novel TRbeta mutations occurring in the same nucleotide. The proposita had two children from each of her two marriages. One daughter and one son from each marriage had severe RTH with free T(4) and T(3) levels 3- to 4-fold the mean normal values and unsuppressed TSH, mental retardation, and deafness. The proposita had a missense mutation (GTG to GGG) in codon 458 of the TRbeta gene, resulting in the replacement of the normal valine with glycine (V458G). Although this mutation was transmitted to her affected son, the mutated codon in her affected daughter was GAG, encoding glutamic acid (V458E). Haplotype analysis showed that this de novo mutation occurred on the already mutant allele of the proposita. Cotransfection of each of these mutant TRbetas with the wild-type TRbeta showed a potent dominant negative effect. Large amounts of T(3) were required to dissociate homodimers of the mutant TRbeta bound to DNA. In addition, and in contrast to other mutant TRbetas with severe T(3)-binding defects, homodimer release failed to recruit the steroid receptor coactivator. No defects in heterodimerization with retinoid X receptor-alpha or association with a nuclear receptor corepressor, were identified. These in vitro data are in agreement with the in vivo phenotype of severe RTH. Unique and previously unreported in human inherited diseases is the occurrence of a de novo mutation at an already mutant nucleotide. Because the occurrence by chance is extremely unlikely, it is postulated that the presence of three guanines in the sequence created by the mutant nucleotide of the proposita results in a mutagenic site prone to de novo mutation.

Adult↗
PubMed2003

The effect of short-term treatment with recombinant human thyroid-stimulating hormones on leydig cell function in men.

High levels of thyroid-stimulating hormone (TSH) have been implicated as a cause for precocious puberty associated with severe long-standing juvenile hypothyroidism. Recombinant human thyroid-stimulating hormone (rhTSH) is available for the management of patients with thyroid carcinoma, and after its administration the serum TSH levels are similar to those observed in hypothyroid infants with precocious puberty. Our objective was to investigate whether rhTSH increased testosterone secretion in adult males with differentiated thyroid carcinoma. Thirty-one adult Caucasian men, ages 18-59 years, with differentiated thyroid carcinoma were studied. While continuing on thyroid hormone therapy, patients received 0.9 mg of rhTSH 24 hours apart. Blood samples were obtained before the first rhTSH dose (day 1) and at 24 hours (day 3) and 72 hours (day 5) after the second rhTSH dose. TSH, total testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined. Serum TSH levels were increased at day 3 (129.2 +/- 5.7 micro U/mL) versus day 1 (0.6 +/- 0.2 micro U/mL) but observed differences in total testosterone, LH and FSH throughout the study were not statistically significant. In conclusion, short-term elevations in serum TSH levels in the range reported in hypothyroid boys with precocious puberty did not increase serum testosterone levels in adult men.

Adult↗
PubMed2002

Leptin and reproductive function in males.

Leptin is a circulating protein produced by adipocytes that has been implicated in control of body weight through appetite regulation and control of reproduction, most likely through an effect on the central nervous system. From studies in mice, it is clear that the genetic background of the animal on which the mutation in the leptin gene is placed can influence how that mutation is expressed. Although the effects of leptin have been more thoroughly documented in nonprimate species than in primates, a few human families with genetic mutations of the gene for leptin or the leptin receptor show obesity and impaired fertility. There is conflicting evidence regarding the effects of leptin in male primates, but it appears that the metabolic and reproductive effects of low leptin levels caused by reduced energy intake in adult animals can be more readily alleviated by administration of energy substrates than by administration of leptin.

Adipocytes↗
PubMed2002

Hypoglycemia-induced suppression of luteinizing hormone (LH) secretion in intact female rhesus macaques: role of vasopressin and endogenous opioids.

The first objective of this study was to determine whether insulin-induced hypoglycemia (IIH) inhibits LH secretion in unrestrained female macaques during the follicular phase of the menstrual cycle. There was a consistent inhibitory effect of hypoglycemia on LH secretion within 3 h in these females. This inhibition was likely an indirect effect since low glucose levels did not inhibit GnRH secretion from GT1-1 neurones in vitro. We next investigated whether administration of a vasopressin antagonist (AVPa) either alone, or with naloxone could reverse the IIH-induced inhibition of LH release. Females were studied in the follicular phase during 10 h periods with blood samples collected every 10 min. Experimental groups were IIH (n=6), IIH+AVPa (n=5) and IIH+AVPa+naloxone (n=4). The first 5 h of each study served as a control and hypoglycemia was then induced with insulin. The AVPa was given as a bolus (180 microg) just before the insulin and was followed by a continuous infusion (180 microg/h) for 5 h. Naloxone (5 mg/kg) was given with the AVPa and followed by a continuous infusion (5 mg/kg/h) for 5 h. In the IIH group, LH reached its lowest value 3-4 h after insulin. Neither AVPa nor AVPa+naloxone infusion reversed the inhibitory action of hypoglycemia on LH release. These data suggest that if there are inhibitory actions of vasopressin and endogenous opioids on GnRH release induced by hypoglycemia, they are not sufficient to explain the suppression of GnRH/LH release in intact female primates.

Animals↗
PubMed2002

Thyroid nodules: diagnosis and therapy.

Less than 1% of all cancers are present in the thyroid, yet thyroid nodules are found in 4 to 10% of the adult population. Because thyroid nodules are relatively common, the diagnostic dilemma is to distinguish between a more common benign nodule, which usually does not require specific treatment, and a malignant nodule, which requires thyroidectomy and further treatment. Thyroid nodules usually are an incidental finding on a routine examination by a primary care physician. When patients seek treatment for symptomatic nodules, a more serious problem may be indicated, and thyroid cancer is suggested. However, additional studies have demonstrated the use of genetic markers and immunohistochemistry in the diagnosis of thyroid nodules, which may lead to a more rational approach to the treatment. This article reviews literature published in the last 12 months pertaining to the pathogenesis, diagnosis, and treatment of thyroid nodules.

Algorithms↗
PubMed2002

Glucose relays information regarding nutritional status to the neural circuits that control the somatotropic, corticotropic, and gonadotropic axes in adult male rhesus macaques.

In male mammals, the neuroendocrine responses to fasting include increased GH and cortisol secretion and suppressed LH and T levels. Because blood glucose levels fall during fasting, we hypothesized that this modest, but consistent, change in blood glucose was a metabolic signal for the neuroendocrine adjustments of reproductive and metabolic hormones. Glucose (D-dextrose, 480 kcal/d) was infused into fasted (48 h) adult male rhesus macaques; and LH, cortisol, and GH were measured in plasma from samples collected at 15-min intervals for the last 15 h of the fast. We analyzed hormone secretion by deconvolution analysis, and the orderliness of release patterns by the approximate entropy statistic. Circulating blood glucose was 76 +/- 7 mg/dl in the fed control group, significantly higher (P < 0.01) than the level of 56 +/- 3 mg/dl in the fasted group. The increase in GH pulsatility and the 2-fold elevation in cortisol levels observed in the fasted male macaques were prevented by parenteral glucose delivery. The suppression of LH in fasted animals was not relieved by glucose infusions but seemed to be partially prevented in three of the animals. These findings are consistent with the hypothesis that glucose serves as a signal of nutritional status controlling adaptive neuroendocrine responses to fasting in the primate.

Adrenocorticotropic Hormone↗