Laron syndrome

Laron syndrome is a rare, genetic, growth hormone insensitivity disorder caused by mutations in the growth hormone receptor gene. Affected patients have severe postnatal growth failure, characteristic facial features, and metabolic abnormalities, including severe obesity and metabolic syndrome. Women with Laron syndrome are usually subfertile, mainly due to obesity and metabolic dysregulation, and require treatment for their chronic reproductive dysfunction. To date, infertility in Laron syndrome patients is a rarely addressed problem and, as a result, adequate data regarding its treatment are lacking...

Autonomy support is a concept that is derived from self-determination theory. Autonomy refers to the freedom to act as one chooses. The current study aimed to examine if autonomy support was associated with dried blood spot validated pre-exposure prophylaxis (PrEP) adherence, and whether the association was mediated by PrEP adherence goal setting and progress toward PrEP adherence goals. Our sample was drawn from Black men who have sex with men (MSM) from across three cities (Chapel Hill, NC; Los Angeles, CA; and Washington, DC) in the United States between February 2013 and September 2014...

AIMS: We examined the effect of growth hormone (GH) counter-regulation on carbohydrate metabolism in individuals with life-long diminished insulin secretion (DIS). METHODS: Adults homozygous for the E180 splice site mutation of GHR [Laron syndrome (LS)], adults with a gain-of-function mutation in CDKN1c [Guevara-Rosenbloom syndrome (GRS)], and controls were evaluated for body composition, leptin, total and high molecular weight (HMW) adiponectin, insulin-like growth factor (IGF) axis molecules, and a 5-hour oral glucose tolerance test (OGTT), with measurements of glucose, insulin, glucagon, ghrelin, pancreatic polypeptide, gastric inhibitory peptide, glucagon-like peptide-1, peptide YY, and islet amyloid polypeptide (IAPP)...

The growth hormone (GH)-insulin-like growth factor (IGF) cascade is central to the regulation of growth and metabolism. This article focuses on the history of the components of the IGF system, with an emphasis on the peptide hormones, IGF-I and -II, their cell surface receptors, and the IGF binding proteins (IGFBPs) and IGFBP proteases that regulate the availability of the peptide hormones for interaction with their receptors in relevant target tissues. We describe landmark events in the evolution of the somatomedin hypothesis, including evidence that has become available from experiments at the molecular and cellular levels, whole animal and tissue-specific gene knockouts, studies of cancer epidemiology, identification of prismatic human cases, and short- and long-term clinical trials of IGF-I therapy in humans...

The growth hormone (GH)-insulin-like growth factor-1 (IGF1) signaling pathway plays a major role in orchestrating cellular interactions, metabolism, growth and aging. Studies from worms to mice showed that downregulated activity of the GH/IGF1 pathway could be beneficial for the extension of lifespan. Laron syndrome (LS) is an inherited autosomal recessive disorder caused by molecular defects of the GH receptor (GHR) gene, leading to congenital IGF1 deficiency. Life-long exposure to minute endogenous IGF1 levels in LS is associated with low stature as well as other endocrine and metabolic deficits...

Pathway involving insulin-like growth factor 1 (IGF-1) plays significant role in growth and development. Crucial role of IGF-1 was discovered inter alia through studies involving deficient patients with short stature, including Laron syndrome individuals. Noteworthy, despite disturbances in proper growth, elevated values for selected stem cell populations were found in IGF-1 deficient patients. Therefore, here we focused on investigating role of these cells-very small embryonic-like (VSEL) and hematopoietic stem cells (HSC), in the pathology...

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Adolescents and sexual minority men (SMM) are high priority groups in the United Nations' 2021 - 2016 goals for HIV prevention and viral load suppression. Interventions aimed at optimizing HIV prevention, testing and viral load suppression for adolescents must also attend to the intersectional realities influencing key sub-populations of SMM. Consequently, there is not a robust evidence-base to guide researchers and program partners on optimal approaches to implementing interventions with adolescent SMM...

Adolescents in sub-Saharan Africa, specifically adolescent girls and young women, young men who have sex with men, transgender persons, persons who use substances, and adolescents experiencing homelessness experience intersectional stigma, have a high incidence of HIV and are less likely to be engaged in HIV prevention and care. We conducted a thematic analysis informed by the Health and Discrimination Framework using a multiple case study design with five case studies in 3 sub-Saharan African countries. Our analysis found commonalities in adolescents' intersectional stigma experiences across cases, despite different contexts...

INTRODUCTION: In Ghana, men who have sex with men (MSM) are estimated to be 11 times more likely to be living with HIV than the general population. Stigmas at the intersection of HIV, same-sex and gender non-conformity are potential key drivers behind this outsized HIV disease burden. Healthcare workers (HCWs) are essential to HIV prevention, care and treatment and can also be sources of stigma for people living with HIV and MSM. This article describes the process and results of adapting an evidence-based HIV stigma-reduction HCW training curriculum to address HIV, same-sex and gender non-conformity stigma among HCWs in the Greater Accra and Ashanti regions, Ghana...

Growth hormone (GH) is a peptide hormone that can signal directly through its receptor or indirectly through insulin-like growth factor 1 (IGF-1) stimulation. GH draws its name from its anabolic effects on muscle and bone but also has distinct metabolic effects in multiple tissues. In addition to its metabolic and musculoskeletal effects, GH is closely associated with aging, with levels declining as individuals age but GH action negatively correlating with lifespan. GH's effects have been studied in human conditions of GH alteration, such as acromegaly and Laron syndrome, and GH therapies have been suggested to combat aging-related musculoskeletal diseases, in part, because of the decline in GH levels with advanced age...

African immigrants in the United States experience disparities in HIV incidence. Pre-exposure prophylaxis (PrEP) effectively prevents HIV infection, yet uptake is low among racial and ethnic minorities. To better understand PrEP adoption among African immigrants, in March 2020, we conducted interviews with Ghanaian immigrants ( N = 40) to explore the barriers and ways to overcome these barriers to PrEP adoption. Participants described several barriers (e.g., low HIV knowledge and risk perception, fear of social judgment, cultural values, and norms), which may impede PrEP adoption...

Normal growth and development in mammals are tightly controlled by numerous genetic factors and metabolic conditions. The growth hormone (GH)-insulin-like growth factor-1 (IGF1) hormonal axis is a key player in the regulation of these processes. Dysregulation of the GH-IGF1 endocrine system is linked to a number of pathologies, ranging from growth deficits to cancer. Laron syndrome (LS) is a type of dwarfism that results from mutation of the GH receptor ( GHR ) gene, leading to GH resistance and short stature as well as a number of metabolic abnormalities...

OBJECTIVE: Chagas disease (CD) is caused by the protozoan parasite, Trypanosoma cruzi. It affects 7 to 8 million people worldwide and leads to approximately 50,000 deaths per year. In vitro and in vivo studies had demonstrated that Trypanosoma cruziinfection causes an imbalance in the hypothalamic-pituitary-adrenal (HPA) axis that is accompanied by a progressive decrease in growth hormone (GH) and prolactin (PRL) production. In humans, inactivating mutations in the GH receptor gene cause Laron Syndrome (LS), an autosomal recessive disorder...

OBJECTIVE: To describe focal epilepsy in patients with Laron syndrome (LS). METHODS: Data were retrieved from medical records of a single-center cohort of 75 patients with LS. RESULTS: We describe for the first time four patients with concomitant focal epilepsy and LS. Two of them experienced episodes of status epilepticus (SE). EEGs in all four patients showed interictal epileptiform discharges (IEDs) in the temporal regions. Three achieved long-term seizure freedom on anti-seizure medications...

The only treatment tested for growth hormone receptor (GHR) defective Laron Syndrome (LS) is injections of recombinant insulin-like-growth factor 1 (rhIGF1). The response is suboptimal and associated with progressive obesity. In this study, we treated 4-5-week-old Laron dwarf mice (GHR-/-) with an adeno-associated virus expressing murine GHR (AAV-GHR) injection at a dose of 4 × 1010 vector genome per mouse. Serum growth hormone (GH) levels decreased, and GH-responsive IGF1, IGF binding protein 3 (IGFBP3) and acid labile subunit (ALS) increased...

Objectives: This study examined factors contributing to decision conflict and the decision support needs of PrEP-eligible Black patients. Methods: The Ottawa Decision Support Framework (ODSF) was used to guide the development of a key informant guide used for qualitative data collection. Black patients assessed by healthcare providers as meeting the basic criteria for starting PrEP were recruited through the St. Michael's Hospital Academic Family Health Team and clinical and community agencies in Toronto. Participants were interviewed by trained research staff...

SEC23B is one of two vertebrate paralogs of SEC23, a key component of the coat protein complex II vesicles. Complete deficiency of SEC23B in mice leads to perinatal death caused by massive degeneration of professional secretory tissues. However, functions of SEC23B in postnatal mice and outside professional secretory tissues are unclear. In this study, we generated a Sec23b KO mouse and a knockin (KI) mouse with the E109K mutation, the most common human mutation in congenital dyserythropoietic anemia type II patients...

Ever since the discoveries that human hair follicles (HFs) display the functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis, exhibit elements of the hypothalamic-pituitary-thyroid axis, and even generate melatonin and prolactin, human hair research has proven to be a treasure chest for the exploration of neurohormone functions. However, growth hormone (GH), one of the dominant neurohormones of human neuroendocrine physiology, remains to be fully explored in this context. This is interesting since it has long been appreciated clinically that excessive GH serum levels induce distinct human skin pathology...

HIV/AIDS disproportionately burdens African immigrants in the United States. Oral pre-exposure prophylaxis (PrEP) is an effective prevention tool for people at high HIV risk, yet uptake is low among racial and ethnic minorities-particularly immigrants. This study explores the awareness, perception, and willingness to use PrEP among Ghanaian immigrants in the United States. WhatsApp, a social media platform, was used to recruit and conduct semi-structured oral interviews with 40 Ghanaian immigrants in March 2020...