Dataset Information

INSL3 Variation in Dogs Following Suppression and Recovery of the HPG Axis.

ABSTRACT: Insulin-like peptide 3 (INSL3) is a constitutive product of mature, adult-type Leydig cells of the testes and consequently in most mammals is an ideal biomarker with which to monitor pubertal development. A new heterologous time-resolved fluorescence immunoassay was developed and validated to measure circulating INSL3 in the blood of adult male dogs. Compared to other species, INSL3 concentration is low with marked variation between individuals, which appears to be independent of breed, age, or weight. A model system was then used in which a cohort of beagle dogs was subject to a GnRH-agonist implant to suppress the HPG axis and spermatogenesis, followed by implant removal and recovery. Unlike testosterone, INSL3 levels were not fully suppressed in all animals by the GnRH agonist, nor was the recovery of Leydig cell function following implant removal uniform or complete, even after several weeks. In dogs, and dissimilar from other species (including humans), Leydig-cell INSL3 appears to be quite variable between individual dogs and only weakly connected to the physiology of the HPG axis after its suppression by a GnRH-agonist implant and recovery. Consequently, INSL3 may be less useful in this species for the assessment of testis function.

SUBMITTER: Anand-Ivell R

PROVIDER: S-EPMC10931505 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

INSL3 Variation in Dogs Following Suppression and Recovery of the HPG Axis.

Anand-Ivell Ravinder R Coutinho Acacia Rebello AR Dai Yanzhenzi Y England Gary G Goericke-Pesch Sandra S Ivell Richard R

Animals : an open access journal from MDPI 20240221 5

Insulin-like peptide 3 (INSL3) is a constitutive product of mature, adult-type Leydig cells of the testes and consequently in most mammals is an ideal biomarker with which to monitor pubertal development. A new heterologous time-resolved fluorescence immunoassay was developed and validated to measure circulating INSL3 in the blood of adult male dogs. Compared to other species, INSL3 concentration is low with marked variation between individuals, which appears to be independent of breed, age, or ...[more]

PMID: 38473059

Similar Datasets

Project description:BackgroundDespite the common use of topical ophthalmic corticosteroids in dogs, detailed reports on systemic and dermatologic adverse effects are limited.ResultsNine purpose-bred research Beagles were treated with difluprednate 0.05% ophthalmic emulsion in one or both eyes 2-3 times daily. Some difluprednate treated dogs developed mild to severe alopecia of the periocular region, face, and distal pinna (5/9). The median duration of treatment prior to onset of dermatologic signs for difluprednate treated dogs was 550 days (453-1160 days). Diagnostic testing included complete blood count (CBC) and serum biochemistry, adrenocorticotropic hormone (ACTH) stimulation testing combined with endogenous ACTH measurement, and skin biopsy. The CBC and chemistry were within normal limits for all dogs. There were varying degrees of suppression of the hypothalamic-pituitary-adrenocortical (HPA) axis with difluprednate treatment. Dogs with the most profound alopecic changes had less pronounced HPA axis suppression compared to dogs with no integumentary changes. Skin biopsies demonstrated follicular atrophy and follicular keratosis. When topical difluprednate was reduced to unilateral therapy, the hair regrew on the untreated side of the face. In addition to the affected research dogs, a 7-year old female spayed Chihuahua that was being treated as a clinical patient with long-term difluprednate 0.05% ophthalmic emulsion developed generalized hypotrichosis on the head and body and a potbellied appearance. ACTH stimulation testing revealed suppression of the HPA axis with a mild increase in serum alkaline phosphatase (ALP) activity and a urine specific gravity of 1.016. The combination of clinical signs and laboratory abnormalities was supportive of iatrogenic hyperadrenocorticism.ConclusionsIn dogs long-term use of difluprednate ophthalmic emulsion results in HPA axis suppression and in some cases iatrogenic hyperadrenocorticism. A novel pattern of localized alopecia is suspected to be related to dermal absorption and local action due to superior potency and penetration compared to other commonly utilized ophthalmic corticosteroids.

Project description:Affective disorders show sex-specific differences in prevalence, symptoms, and complications. One hypothesis for this discrepancy is the interaction between the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis. The present study investigates the influence of androgen on the behavioral phenotype and explores how it interacts with HPA axis genes. Gonadectomized (GDX) and GDX rats treated with testosterone propionate (T) were tested for learned helplessness (LH) behavior and compared with tested controls (TC). Prefrontal cortex was used for analyses of HPG- axis-related genes (androgen receptor, (Ar); estrogen receptor-β (Er-β)) and HPA axis-related genes (corticotropin-releasing hormone, (Crh); glucocorticoid receptor, (Nr3c1); corticotropin-releasing hormone receptor 1, (Crhr1); corticotropin-releasing hormone receptor 2, (Crhr2); FK506 binding protein 5, (Fkbp5)). Promoter-specific CpG methylation in the Crh gene was determined by bisulfite sequencing. Chromatin immunoprecipitation (ChIP) assay was used for determining ER-β binding on the proximal promoter region of Crh gene. Serum testosterone levels confirmed a testosterone-depleted GDX group, a group with supraphysiological levels of testosterone (T) and another group with physiological levels of testosterone (control (C)). Unlike GDX rats, T group exhibited significantly higher LH score when compared with any other group. Crh and Fkbp5 genes were significantly upregulated in GDX group compared with controls, whereas Er-β showed a significant downregulation in the same group. Methylation analysis showed no significant differences in-between groups. ChIP assay was unable to determine a significant change in ER-β binding but revealed a notable contrast in Crh promoter occupancy between T and GDX groups. Altogether, the present study reveals an increased susceptibility to depression-like behavior due to chronic supraphysiological level of androgen via HPA axis inhibition.

Project description:ObjectiveTo describe recovery of adrenal insufficiency in asthmatic children treated with inhaled corticosteroids (ICS) and cortisol replacement therapy.DesignRetrospective, observational study.PatientsA total of 113 patients, 74 male; age 10.4 (3.3-16.5) years; beclomethasone-equivalent ICS dose, 800 μg, (100-1,000), tested by low dose short Synacthen (tetracosactide) test (LDSST), were studied. Test results were classified by basal and peak cortisol concentration: "normal" (basal >100 nmol/L, peak >500 nmol/L), "suboptimal" (basal >100 nmol/L, peak 350-499 nmol/L), "abnormal" (basal <100 nmol/L and/or peak <350 nmol/L). Patients with suboptimal results received hydrocortisone during periods of stress only, and those with abnormal responses received daily hydrocortisone, increased during periods of stress. A total of 73 patients (68%) had ≥2 LDSSTs over 2.2 years (0.2-7.7).MeasurementsChange in cortisol response to repeat LDSST (movement between diagnostic groups, difference in basal and peak cortisol >15% [2× the inter-assay coefficient of variation]), change in BMI and height standard deviation score (SDS).ResultsBaseline test results were abnormal in 17 patients (15%) and all of them had repeat tests. In 13 patients (76%), test results improved (normal in six, suboptimal in seven) and four (24%) remained abnormal. Baseline tests results were suboptimal in 54 patients (48%), of whom 50 (93%) were retested. Repeat tests were normal in 36 patients (72%), remained suboptimal in 11 (22%), and were abnormal in three (6%). Baseline tests results were normal in 42 patients, of whom six patients (14%) were retested. Results remained normal in three (50%), were suboptimal in two (33%), and abnormal in one (17%). Basal and peak cortisol levels increased by >15% in 33/73 (45%) and 42/73 (57%) patients, respectively, and decreased by >15% in 14/73 (19%) and 7/73 (10%), respectively. There was no significant change in height or BMI SDS.ConclusionRecovery of adrenal function is common and occurs during continued ICS and cortisol replacement therapy.

Dataset Information

INSL3 Variation in Dogs Following Suppression and Recovery of the HPG Axis.

Publications

INSL3 Variation in Dogs Following Suppression and Recovery of the HPG Axis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets