Hypogonadism induced by surgical stress and brain trauma is reversed by human chorionic gonadotropin in male rats: A potential therapy for surgical and TBI-induced hypogonadism?

INTRODUCTION: Hypogonadotropic hypogonadism (HH) is an almost universal, yet underappreciated, endocrinological complication of traumatic brain injury (TBI). The goal of this study was to determine whether the developmental hormone human chorionic gonadotropin (hCG) treatment could reverse HH induced by a TBI. METHODS: Plasma samples were collected at post-surgery/post-injury (PSD/PID) days -10, 1, 11, 19 and 29 from male Sprague-Dawley rats (5- to 6-month-old) that had undergone a Sham surgery (craniectomy alone) or CCI injury (craniectomy + bilateral moderate-to-severe CCI injury) and treatment with saline or hCG (400 IU/kg; i.m.) every other day. RESULTS: Both Sham and CCI injury significantly decreased circulating testosterone (T), 11-deoxycorticosterone (11-DOC) and corticosterone concentrations to a similar extent (79.1% vs. 80.0%; 46.6% vs. 48.4%; 56.2% vs. 32.5%; respectively) by PSD/PID 1. hCG treatment  returned circulating T to baseline concentrations by PSD/PID 1 (8.9 ± 1.5 ng/ml and 8.3 ± 1.9 ng/ml; respectively) and was maintained through PSD/PID 29. hCG treatment significantly, but transiently, increased circulating progesterone (P4) ~3-fold (30.2 ± 10.5 ng/ml and 24.2 ± 5.8 ng/ml) above that of baseline concentrations on PSD 1 and PID 1, respectively. hCG treatment did not reverse hypoadrenalism following either procedure. CONCLUSIONS: Together, these data indicate that (1) craniectomy is sufficient to induce persistent hypogonadism and hypoadrenalism, (2) hCG can reverse hypogonadism induced by a craniectomy or craniectomy +CCI injury, suggesting that (3) craniectomy and CCI injury induce a persistent hypogonadism by decreasing hypothalamic and/or pituitary function rather than testicular function in male rats. The potential role of hCG as a cheap, safe and readily available treatment for reversing surgery or TBI-induced hypogonadism is discussed.

A retrospective review of canine benign prostatic hyperplasia with and without prostatitis.

Benign prostatic hyperplasia (BPH) is the most common prostatic disorder in older intact male dogs, but despite its prevalence, there are inconsistencies in clinical diagnosis and treatment. Although prostate size was historically considered the hallmark feature of BPH in men, currently, there is only a weak correlation between prostate size and clinical severity. We performed a retrospective cohort study with the primary objective of assessing clinical signs, ultrasonographic findings, treatments, and outcomes in dogs diagnosed with BPH, with and without concurrent prostatitis. We reviewed medical records and obtained data on presenting signs, prostatic imaging, and prevalence of concurrent bacteriuria. Prostate size was determined by ultrasonography and compared to the calculated expected size based on patient age and weight. Treatment and outcome were described for the cases with a minimum 2 months follow-up. Median age of dogs diagnosed with BPH was 8 years. Clinical signs were present in 16/25 dogs and scored as mild to moderate (median Zambelli's Symptom Index for BPH score 12). The median prostatic volume to body mass ratio was 1.60 mm3/kg. Prostate size did not correlate with the symptom severity. Concurrent bacteriuria was confirmed in 4/25 cases via bacterial culture and/or cytology. Treatments pursued and responses were only available in a subpopulation of dogs (n = 9) and were highly variable. Studies are needed to determine if current treatment options for BPH in dogs resolve associated clinical signs in addition to reducing prostate size.

An immunohistochemical prostate cell identification key indicates that aging shifts procollagen 1A1 production from myofibroblasts to fibroblasts in dogs prone to prostate-related urinary dysfunction.

BACKGROUND: The identity and spatial distribution of prostatic cell types has been determined in humans but not in dogs, even though aging- and prostate-related voiding disorders are common in both species and mechanistic factors, such as prostatic collagen accumulation, appear to be shared between species. In this publication we characterize the regional distribution of prostatic cell types in the young intact dog to enable comparisons with human and mice and we examine how the cellular source of procollagen 1A1 changes with age in intact male dogs. METHODS: A multichotomous decision tree involving sequential immunohistochemical stains was validated for use in dog and used to identify specific prostatic cell types and determine their distribution in the capsule, peripheral, periurethral and urethral regions of the young intact canine prostate. Prostatic cells identified using this technique include perivascular smooth muscle cells, pericytes, endothelial cells, luminal, intermediate, and basal epithelial cells, neuroendocrine cells, myofibroblasts, fibroblasts, fibrocytes, and other hematolymphoid cells. To enhance rigor and transparency, all high resolution images (representative images shown in the figures and biological replicates) are available through the GUDMAP database at https://doi.org/10.25548/16-WMM4. RESULTS: The prostatic peripheral region harbors the largest proportion of epithelial cells. Aging does not change the density of hematolymphoid cells, fibroblasts, and myofibroblasts in the peripheral region or in the fibromuscular capsule, regions where we previously observed aging- and androgen-mediated increases in prostatic collagen abundance Instead, we observed aging-related changes the procollagen 1A1 positive prostatic cell identity from a myofibroblast to a fibroblast. CONCLUSIONS: Hematolymphoid cells and myofibroblasts are often identified as sources of collagen in tissues prone to aging-related fibrosis. We show that these are not the likely sources of pathological collagen synthesis in older intact male dogs. Instead, we identify an aging-related shift in the prostatic cell type producing procollagen 1A1 that will help direct development of cell type and prostate appropriate therapeutics for collagen accumulation.

Correction: Conjugated Linoleic Acid Administration Induces Amnesia in Male Sprague Dawley Rats and Exacerbates Recovery from Functional Deficits Induced by a Controlled Cortical Impact Injury.

[This corrects the article DOI: 10.1371/journal.pone.0169494.].

Conjugated Linoleic Acid Administration Induces Amnesia in Male Sprague Dawley Rats and Exacerbates Recovery from Functional Deficits Induced by a Controlled Cortical Impact Injury.

Long-chain polyunsaturated fatty acids like conjugated linoleic acids (CLA) are required for normal neural development and cognitive function and have been ascribed various beneficial functions. Recently, oral CLA also has been shown to increase testosterone (T) biosynthesis, which is known to diminish traumatic brain injury (TBI)-induced neuropathology and reduce deficits induced by stroke in adult rats. To test the impact of CLA on cognitive recovery following a TBI, 5-6 month old male Sprague Dawley rats received a focal injury (craniectomy + controlled cortical impact (CCI; n = 17)) or Sham injury (craniectomy alone; n = 12) and were injected with 25 mg/kg body weight of Clarinol® G-80 (80% CLA in safflower oil; n = 16) or saline (n = 13) every 48 h for 4 weeks. Sham surgery decreased baseline plasma progesterone (P4) by 64.2% (from 9.5 ± 3.4 ng/mL to 3.4 ± 0.5 ng/mL; p = 0.068), T by 74.6% (from 5.9 ± 1.2 ng/mL to 1.5 ± 0.3 ng/mL; p < 0.05), 11-deoxycorticosterone (11-DOC) by 37.5% (from 289.3 ± 42.0 ng/mL to 180.7 ± 3.3 ng/mL), and corticosterone by 50.8% (from 195.1 ± 22.4 ng/mL to 95.9 ± 2.2 ng/mL), by post-surgery day 1. CCI injury induced similar declines in P4, T, 11-DOC and corticosterone (58.9%, 74.6%, 39.4% and 24.6%, respectively) by post-surgery day 1. These results suggest that both Sham surgery and CCI injury induce hypogonadism and hypoadrenalism in adult male rats. CLA treatment did not reverse hypogonadism in Sham (P4: 2.5 ± 1.0 ng/mL; T: 0.9 ± 0.2 ng/mL) or CCI-injured (P4: 2.2 ± 0.9 ng/mL; T: 1.0 ± 0.2 ng/mL, p > 0.05) animals by post-injury day 29, but rapidly reversed by post-injury day 1 the hypoadrenalism in Sham (11-DOC: 372.6 ± 36.6 ng/mL; corticosterone: 202.6 ± 15.6 ng/mL) and CCI-injured (11-DOC: 384.2 ± 101.3 ng/mL; corticosterone: 234.6 ± 43.8 ng/mL) animals. In Sham surgery animals, CLA did not alter body weight, but did markedly increase latency to find the hidden Morris Water Maze platform (40.3 ± 13.0 s) compared to saline treated Sham animals (8.8 ± 1.7 s). In CCI injured animals, CLA did not alter CCI-induced body weight loss, CCI-induced cystic infarct size, or deficits in rotarod performance. However, like Sham animals, CLA injections exacerbated the latency of CCI-injured rats to find the hidden MWM platform (66.8 ± 10.6 s) compared to CCI-injured rats treated with saline (30.7 ± 5.5 s, p < 0.05). These results indicate that chronic treatment of CLA at a dose of 25 mg/kg body weight in adult male rats over 1-month 1) does not reverse craniectomy- and craniectomy + CCI-induced hypogonadism, but does reverse craniectomy- and craniectomy + CCI-induced hypoadrenalism, 2) is detrimental to medium- and long-term spatial learning and memory in craniectomized uninjured rats, 3) limits cognitive recovery following a moderate-severe CCI injury, and 4) does not alter body weight.