Darwin Omar Larco

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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(More)
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(More)
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. Adult OVX Sprague-Dawley rats were randomly assigned to one of(More)
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 3.4.24.15 (EP24.15), can cleave GnRH at the Tyr(5)-Gly(6) bond to form the pentapeptide, GnRH-(1-5). The central and peripheral effect(More)
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(More)
The decapeptide GnRH is an important regulator of reproductive behavior and function. In the extracellular matrix, GnRH is metabolized by the endopeptidase EC3.4.24.15 (EP24.15) to generate the pentapeptide GnRH-(1-5). In addition to its expression in the adult hypothalamus, EP24.15 is expressed along the migratory path of GnRH-expressing neurons during(More)
In the extracellular space, the gonadotropin-releasing hormone (GnRH) is metabolized by the zinc metalloendopeptidase EC3.4.24.15 (EP24.15) to form the pentapeptide, GnRH-(1-5). GnRH-(1-5) diverges in function and mechanism of action from GnRH in the brain and periphery. GnRH-(1-5) acts on the orphan G protein-coupled receptor 101 (GPR101) to sequentially(More)
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(More)
The purpose of this study was to evaluate the effects of stress and estradiol (E2) on pain tolerance. Ovariectomized rats were assigned to treatment groups based on a 2 x 4 factorial design comprising stress (nonstress x stress) and hormone treatment vehicle x E2 [0.25 mg/kg/d]) x estrogen receptor alpha (ERalpha)-selective agonist propyl pyrazole triol (1(More)
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(More)