Adrenocortical Challenge Response and Genomic Analyses in Scottish Terriers with Increased Alkaline Phosphate Activity

dataset

posted on 2025-04-16, 19:21 authored by Kurt ZimmermanKurt Zimmerman, David Panciera, Ina Hoeschele, W. Edward Monroe, Stephanie ToddStephanie Todd, Stephen R. Werre, Tanya LeRoithTanya LeRoith, Kellie Fecteau, Bathilda B. Lake

Scottish terriers (ST) frequently have increased serum alkaline phosphatase (ALP) of the steroid isoform. Many of these also have high serum concentrations of adrenal sex steroids. The study's objective was to determine the cause of increased sex steroids in ST with increased ALP. Adrenal gland suppression and stimulation were compared by low dose dexamethasone (LDDS), human chorionic gonadotropin (HCG) and adrenocorticotropic hormone (ACTH) response tests. Resting plasma pituitary hormones were measured. Steroidogenesis-related mRNA expression was evaluated in six ST with increased ALP, eight dogs of other breeds with pituitary-dependent hyperadrenocorticism (HAC), and seven normal dogs. The genome-wide association of single nucleotide polymorphisms (SNP) with ALP activity was evaluated in 168 ST. ALP (reference interval 8–70 U/L) was high in all ST (1,054 U/L) and HAC (985 U/L) dogs. All HAC dogs and 2/8 ST had increased cortisol post-ACTH administration. All ST and 2/7 Normal dogs had increased sex steroids post-ACTH. ST and Normal dogs had similar post-challenge adrenal steroid profiles following LDDS and HCG. Surprisingly, mRNA of hydroxysteroid 17-beta dehydrogenase 2 (HSD17B2) was lower in ST and Normal dogs than HAC. HSD17B2 facilities metabolism of sex steroids. A SNP region was identified on chromosome 5 in proximity to HSD17B2 that correlated with increased serum ALP. ST in this study with increased ALP had a normal pituitary-adrenal axis in relationship to glucocorticoids and luteinizing hormone. We speculate the identified SNP and HSD17B2 gene may have a role in the pathogenesis of elevated sex steroids and ALP in ST.

History

Publisher

University Libraries, Virginia Tech

Corresponding Author Name

Kurt Zimmerman

Corresponding Author E-mail Address

kzimmerm@vt.edu

Files/Folders in Dataset and Description

Part 1 Group data.xlsx: Signalment and ID info on the HAC, Scottish terriers and control dogs used for part 1 endocrine study and part 2 RNA study. Part 2 Group Lab data.xlsx: File shows age, sex, alp and bilirubin values on the 168 Scottish terriers used for the part 2 DNA study (see part 2 DNA file for). Part 1 Lab Endocrine data.xlsx: Routine lab along with endocrine/adrenal data following LDDS, ACTH, and HCG challenge testing. Part 2 RNA data.xlsx: RNA data used to compare HAC, Normal and Scottish terriers groups shown in the part 1 group file. Part 2 DNA data.txt: DNA data used for SNP and GWAS study using Scottish terrier dogs as described in the part 2 group file.