Publications by authors named "Darwin O Larco"

Article Synopsis
  • Poor sleep hygiene negatively impacts various biological systems, especially through dysfunction in the pituitary gland, which regulates sleep and stress responses.
  • A study analyzed gene expression changes in mice after 12 hours of sleep deprivation, followed by a stress test, revealing significant differences in gene expression related to hormone secretion and the stress response.
  • The findings highlighted sex-specific differences in gene responses, with a notable increase in differentially expressed genes after sleep deprivation followed by stress, suggesting potential genetic targets for understanding sleep and stress interactions.
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Gonadotropin-releasing hormone (GnRH) neurons originate outside the central nervous system (CNS) in the nasal placode where their migration to the basal forebrain is dependent on the integration of multiple signaling cues during development. The proper migration and establishment of the GnRH neuronal population within the CNS are critical for normal pubertal onset and reproductive function. The endopeptidase EP24.

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17β-Estradiol is known to regulate energy metabolism and body weight. Ovariectomy results in body weight gain while estradiol administration results in a reversal of weight gain. Isoflavones, found in rodent chow, can mimic estrogenic effects making it crucial to understand the role of these compounds on metabolic regulation.

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Article Synopsis
  • Phytoestrogens, particularly isoflavones found in rodent diets, mimic estrogen and can disrupt endocrine functions by influencing estrogen receptors.
  • In ovariectomized (OVX) rats, the presence of isoflavones altered the effects of 17β-estradiol (E2), showing that E2 caused anxiety when isoflavones were included, but reduced anxiety when they weren't.
  • Additionally, E2 promoted antidepressant-like behaviors and increased BDNF expression in the hippocampus, amygdala, and hypothalamus only when isoflavones were part of the diet, highlighting their role in modulating hormonal effects on behavior.
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We recently showed that Xq26.3 microduplications cause X-linked acrogigantism (X-LAG). X-LAG patients mainly present with growth hormone and prolactin-secreting adenomas and share a minimal duplicated region containing at least four genes.

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Cushing disease (CD) in children is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Germline or somatic mutations in genes such as MEN1, CDKIs, AIP, and USP8 have been identified in pediatric CD, but the genetic defects in a significant percentage of cases are still unknown. We investigated the orphan G protein-coupled receptor GPR101, a gene known to be involved in somatotropinomas, for its possible involvement in corticotropinomas.

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In the extracellular space, the gonadotropin-releasing hormone (GnRH) is metabolized by the zinc metalloendopeptidase EC3.4.24.

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Given the central role of the decapeptide gonadotropin-releasing hormone (GnRH) in reproductive function, our long-term objective is to delineate the underlying mechanism regulating these reproductive processes. The outcome of GnRH secretion is in part dependent on the proteolytic metabolism of this decapeptide. In contrast to the belief that the metabolism of GnRH serves only as a degradative process that removes excess GnRH, we have shown that a metabolite of the decapeptide, GnRH-(1-5), can directly regulate GnRH gene expression and reproductive behavior.

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Background: Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood.

Methods: We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly.

Results: We observed microduplication on chromosome Xq26.

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The decapeptide GnRH is known for its central role in the regulation of the hypothalamo-pituitary-gonadal axis. In addition, it is also known to have local effects within peripheral tissues. The zinc metalloendopeptidase, EC 3.

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We have previously demonstrated that the cleavage product of the full-length GnRH, GnRH-(1-5), is biologically active, binds G protein-coupled receptor 173 (GPR173), and inhibits the migration of cells in the immortalized GnRH-secreting GN11 cell. In this study, we attempted to characterize the GnRH-(1-5) intracellular signaling mechanism. To determine whether the signaling pathway mediating GnRH-(1-5) regulation of migration involves a G protein-dependent mechanism, cells were treated with a generic G protein antagonist in the presence and absence of GnRH-(1-5), and a wound-healing assay was conducted to measure migration.

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The gonadotropin-releasing hormone (GnRH) was originally isolated from the mammalian hypothalamus for its role as the primary regulator of reproductive function. Since its discovery, GnRH has also been shown to be located in non-hypothalamic tissues and is known to have diverse functions. Although the regulation of GnRH synthesis and release has been extensively studied, there is additional evidence to suggest that the processing of GnRH to the metabolite GnRH-(1-5) represents another layer of regulation.

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The decapeptide GnRH is an important regulator of reproductive behavior and function. In the extracellular matrix, GnRH is metabolized by the endopeptidase EC3.4.

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Previous studies have shown that both 17β-estradiol (E2) treatment and chronic stress may attenuate post-OVX weight gain in the female rat. However, the interaction between E2 and stress is unclear. This study examined the effect of E2 treatment and chronic immobilization stress on body weight.

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Objective: The objective of this study was to distinguish the role of specific estrogen receptors (ERs), ERalpha and ERbeta, on body weight regulation using a rat model of weight gain subsequent to menopause.

Study Design: Ovariectomized rats were utilized as the animal model to simulate the postmenopause weight gain. The rats were ovariectomized and subcutaneously injected daily with vehicle, estradiol-17beta (E2), propylpyrazoletriol (PPT; ERalpha agonist) and diarylpropionitrile (DPN; ERbeta agonist).

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