Regulation of gene expression in Sertoli cells by follicle-stimulating hormone (FSH): Cloning and characterization of LRPR1, a primary response gene encoding a leucine-rich protein

Searching for hormone-regulated genes in testicular Sertoli cells, we cloned and sequenced a cDNA of 3108 base pairs, named LRPR1 (signifying leucine-rich primary response gene 1). This cDNA sequence has an open reading frame of 2238 base pairs encoding a leucine-rich protein of 746 amino acid residues with a relative molecular mass of 85.6 kDa. As much as 16% of the amino acid residues is leucine. Database analysis revealed significant similarity of LRPR1 to the human brain cDNA sequence EST00443, but not to any other sequences present in databases. The expression of LRPR1 mRNA in Sertoli cells is strongly and rapidly up-regulated by follicle-stimulating hormone (FSH). The level of LRPR1 mRNA was very low in Sertoli cells isolated from 21-day-old rats and cultured for 3 days in the absence of FSH, but LRPR1 mRNA expression was markedly increased within 2 h after addition of FSH to these cultures. A maximal response was reached within 4 h. Dibutyryl-cyclic AMP [(Bu)2cAMP] and forskolin had similar effects compared to FSH, indicating that cAMP acts as a second messenger in the regulation of LRPR1 expression. The up-regulation of LRPR1 mRNA expression by FSH was also observed in the presence of the protein synthesis inhibitor cycloheximide, indicating that FSH regulates LRPR1 mRNA expression through a direct mechanism which does not require de novo protein synthesis. Thus, LRPR1 represents a primary response gene in FSH action on Sertoli cells. The presently available data indicate that LRPR1 mRNA expression is regulated specifically by FSH, since several other hormones and growth factors did not affect LRPR1 mRNA expression in the cultured Sertoli cells. LRPR1 mRNA expression is relatively high in testis, ovary and spleen. A much lower mRNA level was found in brain and lung, and no expression was detected in liver, kidney, heart, muscle, pituitary gland, prostate, epididymis and seminal vesicle. The basal level of testicular LRPR1 expression in intact 21-day-old rats was markedly increased within several hours after a single i.p. injection of FSH, indicating that in vivo LRPR1 mRNA expression may appear to be a useful parameter to evaluate testicular FSH action

Prevalence and Determinants of Pain in Spinal Cord Injury During Initial Inpatient Rehabilitation:Data From the Dutch Spinal Cord Injury Database

Objective: To describe the prevalence and characteristics of spinal cord injury (SCI)-related pain during initial inpatient rehabilitation and to investigate relationships with demographic and lesion characteristics. Design: Cohort during inpatient rehabilitation. Setting: Eight specialized SCI rehabilitation centers in the Netherlands. Participants: Patients with newly acquired SCI admitted for inpatient rehabilitation between November 2013 and August 2019 (N=1432). Interventions: Not applicable. Main Outcome Measures: Presence of pain at admission and discharge. Logistic regression analyses were used to study the prevalence of pain related to sex, age, etiology, completeness, and level of injury. Results: Data from 1432 patients were available. Of these patients 64.6% were male, mean age was 56.8 years, 59.9% had a nontraumatic SCI, 63.9% were classified as American Spinal Cord Injury Association Impairment Scale (AIS) D and 56.5% had paraplegia. Prevalence of pain was 61.2% at admission (40.6% nociceptive pain [NocP], 30.2% neuropathic pain [NeuP], 5.4% other pain) and 51.5% at discharge (26.0% NocP, 31.4% NeuP, 5.7% other pain). Having NocP at admission was associated with traumatic SCI. AIS B had a lower risk of NocP than AIS D at admission. Having NocP at discharge was associated with female sex and traumatic SCI. AIS C had a lower risk of NocP at discharge than AIS D. Having NeuP at admission was associated with female sex. Having NeuP at discharge was associated with female sex, age younger than 65 years vs age older than 75 years and tetraplegia. Conclusions: SCI-related pain is highly prevalent during inpatient rehabilitation. Prevalence of NocP decreased during inpatient rehabilitation, and prevalence of NeuP stayed the same. Different patient and lesion characteristics were related to the presence of SCI-related pain. Healthcare professionals should be aware of these differences in screening patients on presence and development of pain during inpatient rehabilitation

Labour market participation after spinal cord injury. A register-based cohort study

Study design: A register based cohort study. Objectives: To investigate labour market participation following spinal cord injury (SCI) and to describe the impact of personal and SCI characteristics. Setting: Norway. Methods: Persons registered with SCI in the Norwegian SCI registry 2011–2017, and matched reference individuals without SCI from the general population (named controls) were followed for up to six years after injury using national registry data on employment, education, income, and social security benefits. Main measures of labour market participation were: (1) Receiving any amount of pay for work, and (2) Receiving sickness and disability benefits. Results: Among the 451 persons with SCI (aged 16–66 years and working before injury), the estimated percentages receiving pay for work and sickness and disability benefits in the sixth years after injury were 63% (95% CI 57–69) and 67% (95% CI 61–72). Corresponding percentages for the controls (n = 1791) were 91% (95% CI 90–93) for receiving pay for work and 13% (95% CI 12–15) for receiving sickness and disability benefits. Among persons with SCI, less severe neurological outcome, higher level of education, younger age at injury, and a stronger pre-injury attachment to employment (higher employment income, having an employer, less receipt of benefits), were associated with higher labour market participation. Conclusion: SCI substantially decreased labour market participation up to six years after injury compared to matched controls. Even if a relatively large proportion of persons with SCI remained in some degree of work activity, more than half did so in combination with receiving benefits.</p

Relationship between secondary health conditions and life satisfaction in persons with spinal cord injury:study across twenty-one countries

Purpose: To determine the relationships between impact of secondary health conditions (SHCs), treatment of SHCs, and life satisfaction (LS) following spinal cord injury (SCI) across 21 countries. Hypotheses were as follows: (1) Persons with SCI and fewer SHCs report higher LS and (2) Persons who receive treatment for SHCs report higher LS than those who do not receive treatment.Methods: Cross-sectional survey, including 10,499 persons with traumatic or non-traumatic SCI aged 18 years or older and living in the community. To assess SHCs, 14 items adapted from the SCI-Secondary Conditions Scale were used (range 1–5). SHCs index was calculated as the mean of all 14 items. LS was assessed using a selection of 5 items from the World Health Organization Quality of Life Assessment. LS index was calculated as the mean of these 5 items. Results: South Korea, Germany, and Poland exhibited the highest (2.40–2.93) and Brazil, China, and Thailand the lowest (1.79–1.90) impact of SHCs. Indexes for LS and SHCs were inversely correlated (– 0.418; p &lt; 0.001). Mixed Model Analysis showed that the fixed effect (key predictors of the study) of SHCs index (p &lt; 0.001) and the positive interaction between SHCs index and treatment (p = 0.002) were significant determinants of LS.Conclusion: Persons with SCI across the world are more likely to perceive better LS if they experience fewer SHCs and receive treatment for SHCs, in comparison to those who do not. Prevention and treatment of SHCs following SCI should be a high priority in order to improve the lived experience and enhance LS.</p

Transient down-regulation of androgen receptor messenger ribonucleic acid (mRNA) expression in Sertoli cells by follicle-stimulating hormone is followed by up-regulation of androgen receptor mRNA and protein

In Sertoli cells from 21-day-old rats, the expression of the mRNA encoding the alpha-subunit of inhibin, and the production of immunoreactive inhibin are stimulated by follicle-stimulating hormone (FSH). In contrast, the amount of beta B-subunit mRNA is not increased after FSH treatment of the cells, and the ratio between bioactive and immunoactive inhibin decreases after stimulation with FSH. These data suggest that the beta B-subunit is the limiting factor in the production of bioactive inhibin. The aim of the present experiments was to investigate the effect of changes in the amount of beta B-subunit mRNA on the production of bioactive and immunoreactive inhibin. During early postnatal testicular development, the relative amounts of the 4.2 kb and 3.5 kb mRNAs encoding the beta B-subunit of inhibin changed markedly. The meaning of this changing ratio between beta B-subunit mRNAs is not clear, since both mRNAs are actively translated, as demonstrated by polysomal analysis. The total amount of beta B-subunit mRNA correlated with the in vitro production of bioactive inhibin as published earlier. Prolonged stimulation of cultured Sertoli cells from 14-day-old rats with 4 beta-phorbol 12-myristate 13-acetate (PMA) caused a decreased expression of the beta B-subunit mRNAs, presumably by down-regulation of protein kinase C. A similar effect was obtained after addition of the calcium ionophore A23187. Concomitantly, a decreased production of bioactive inhibin was observed. Furthermore, Western blotting revealed that secr

Using self-regulation assessment to explore associations between self-regulation, participation and health-related quality of life in a rehabilitation population

Objective: Self-regulation, participation and health-related quality of life are important rehabilitation outcomes. The aim of this study was to explore associations between these outcomes in a multi-diagnostic and heterogenic group of former rehabilitation patients.Methods: This cross-sectional survey used the Self-Regulation Assessment (SeRA), Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-Participation) and the Patient-Reported-Outcome-Measurement-System (PROMIS) ability and PROMIS satisfaction with participation in social roles, and the EuroQol-5L-5D and PROMIS-10 Global Health. Regression analyses, controlling for demographic and condition-related factors, were performed.Results: Respondents (n=563) had a mean age of 56.5 (standard deviation (SD) 12.7) years. The largest diagnostic groups were chronic pain disorder and brain injury. In addition to demographic and condition-related factors, self-regulation subscales explained 0–15% of the variance in participation outcome scores, and 0–22% of the variance in HRQoL outcome scores. Self-regulation subscales explained up to 22% of the variance in satisfaction subscales of participation (USER-Participation and PROMIS) and the mental health subscale of the PROMIS-10. Self-regulation subscales explained up to 11% of the restriction and frequency subscales of participation (USER-Participation) and the physical health subscale of the PROMIS-10.Conclusion: Self-regulation is more strongly associated with outcomes such as satisfaction with participation and mental health compared with outcomes such as restrictions in participation and physical health.</p