Experimenting with arts-based methods and affective provocations to understand complex lived experience of a diagnosis of borderline personality disorder.

This article draws on arts-based psycho-social research to explore embodied and visceral knowing and feeling in the context of people living with a diagnosis of borderline personality disorder (BPD). It presents a discussion of creative artworks solicited through a nation-wide online survey conducted in Australia in 2021 that generated intimate and affective understanding about living with a diagnosis of BPD. To investigate what lived experiences of distress associated with a BPD diagnosis communicate through sensation, emotion, image and affective capacity, the authors put to work Blackman's (2015) concept of "productive possibilities of negative states of being" and the broader theoretical framework of new materialism. This approach allows a more transformative feeling-with that exceeds the normative affective repertoires and scripts associated with a diagnosis of BPD. The authors recognise the often unspoken and invisible affects of complex mental distress and trauma, and purposefully open the space for affective and symbolic aspects of creative artworks to communicate what is less known or has less presence in dominant biomedical frameworks about living with a BPD diagnosis. The article foregrounds the lived and living experience of participants to generate experiential rather than clinical understandings of the diagnosis.

A visit with Viv: Empathising with a digital human character embodying the lived experiences of dementia.

The Visit, an immersive participatory artwork (viewed on a screen or virtual reality headset), was produced as part of a research programme investigating the subjective experience of dementia and the relational dynamic between people with dementia and others. It invites viewers to engage with a digital human character, 'Viv', as she shares her experiences of living with dementia. The experiences that Viv recounts are based on verbatim accounts from in-depth interviews with four women living with dementia. The artwork was designed with the combined aim of generating insights into the lived experience of dementia and establishing conditions under which viewers might cultivate empathy for the character portrayed. Viewers engaging with Viv were invited to complete pre- and post-engagement measures of state empathy alongside an assessment of emotional distance. State empathy was significantly greater after engaging with The Visit, and correspondingly, there was a significant decrease in emotional distance (aversion), suggesting that the aims were met.

Edge of the Present: A Virtual Reality Tool to Cultivate Future Thinking, Positive Mood and Wellbeing.

Depression and suicidality are characterized by negative imagery as well as impoverished positive imagery. Although some evidence exists supporting the link between positive imagery and enhanced mood, much work needs to be done. This study explored the impact of an immersive virtual reality experience (Edge of the Present-EOTP) on an individual's mood, state of well-being, and future thinking. Using a 10-min mixed reality experience, 79 individuals explored virtual landscapes within a purposefully built, physical room. A pre and post survey containing mental health measures were administered to each participant. An optional interview following the virtual work was also conducted. The results indicated that positive mood and well-being increased significantly post-intervention. Hopelessness scores and negative mood decreased, whilst sense of presence was very high. This pilot study is among the first to assess the feasibility of a mixed reality experience as a potential platform for depression and suicide prevention by increasing well-being and mood as well as decreasing hopelessness symptoms.

Women and Stigma: A Protocol for Understanding Intersections of Experience through Body Mapping.

This paper outlines a research and dissemination protocol to be undertaken with specific groups of marginalised women in Australia. Women impacted by significant mental distress, disability, or refugee status are among society's most vulnerable and disenfranchised groups. They can experience significant social exclusion, marginalisation and stigma, associated with reduced help seeking, deprivation of dignity and human rights, and threats to health, well-being and quality of life. Previous research has assessed the experiences of discrete groups of women but has to date failed to consider mental health-refugee-disability intersections and overlaps in experience. Using body mapping, this research applies an intersectional approach to identify how women impacted by significant mental distress, disability, and refugee status negotiate stigma and marginalisation. Findings on strategies to cope with, negotiate and resist stigmatised identities will inform health policy and yield targeted interventions informed by much-needed insights on women's embodied experience of stigma. The women's body maps will be exhibited publicly as part of an integrated knowledge translation strategy. The aim is to promote and increase sensitivity and empathy among practitioners and policy makers, strengthening the basis for social policy deliberation.

Mnemoscape: Supporting Older Adults' Event Memory Using Wearable Camera Photographs on an Immersive Interface.

BACKGROUND: Wearable camera photographs have been shown to be an effective memory aid in people with and without memory impairment. Most studies using wearable cameras as a memory aid have presented photographs on a computer monitor and used a written diary or no review as a comparison. In this pioneering study, we took a new and innovative approach to wearable camera photograph review that embeds the photographs within a virtual landscape. This approach may enhance these benefits by reinstating the original environmental context to increase participants' sense of re-experiencing the event. OBJECTIVE: We compare the traditional computer monitor presentation of wearable camera photographs and actively taken digital photographs with the presentation of wearable camera photographs in a new immersive interface that reinstates the spatiotemporal context. METHODS: Healthy older adults wore wearable or took digital photographs during a staged event. The next day and 2 weeks later, they viewed wearable camera photographs on a computer monitor or in context on an immersive interface, or digital photographs. RESULTS: Participants who viewed wearable camera photographs in either format recalled more details during photo viewing and subsequent free recall than participants who viewed digital photographs they had taken themselves. CONCLUSION: Wearable camera photographs are an effective support for event memory, regardless of whether they are presented in context in an experience-near format.

The effects of partnered exercise on physical intimacy in couples coping with prostate cancer.

OBJECTIVE: The study examined whether couples coping with prostate cancer participating in a partnered exercise program-Exercising Together (ET)-experienced higher levels of physical intimacy (i.e., affectionate and sexual behavior) than couples in a usual care (UC) control group. METHOD: Men and their wives (n = 64 couples) were randomly assigned to either the ET or UC group. Couples in the ET group engaged in partnered strength-training twice weekly for 6 months. Multilevel modeling was used to explore the effects of ET on husband and wife engagement in both affectionate and sexual behaviors over time. RESULTS: Controlling for relationship quality, wives in ET showed significant increases in engagement in affectionate behaviors compared to wives in UC. No intervention effects were found for husbands. CONCLUSION: Couple-based approaches to physical intimacy, after a cancer diagnosis, that facilitate collaborative engagement in nonsexual physical activities for the couple have potential to be effective for wives. More research is needed in this area to determine couples most amenable to such exercise strategies, optimal timing in the cancer trajectory, and the benefits of combining partnered exercise with more traditional relationship-focused strategies.

Benefits of partnered strength training for prostate cancer survivors and spouses: results from a randomized controlled trial of the Exercising Together project.

BACKGROUND: Prostate cancer can negatively impact quality of life of the patient and his spouse caregiver, but interventions rarely target the health of both partners simultaneously. We tested the feasibility and preliminary efficacy of a partnered strength training program on the physical and mental health of prostate cancer survivors (PCS) and spouse caregivers. METHODS: Sixty-four couples were randomly assigned to 6 months of partnered strength training (Exercising Together, N = 32) or usual care (UC, N = 32). Objective measures included body composition (lean, fat and trunk fat mass (kg), and % body fat) by DXA, upper and lower body muscle strength by 1-repetition maximum, and physical function by the physical performance battery (PPB). Self-reported measures included the physical and mental health summary scales and physical function and fatigue subscales of the SF-36 and physical activity with the CHAMPS questionnaire. RESULTS: Couple retention rates were 100 % for Exercising Together and 84 % for UC. Median attendance of couples to Exercising Together sessions was 75 %. Men in Exercising Together became stronger in the upper body (p < 0.01) and more physically active (p < 0.01) than UC. Women in Exercising Together increased muscle mass (p = 0.05) and improved upper (p < 0.01) and lower body (p < 0.01) strength and PPB scores (p = 0.01) more than UC. CONCLUSIONS: Exercising Together is a novel couples-based approach to exercise that was feasible and improved several health outcomes for both PCS and their spouses. IMPLICATIONS FOR CANCER SURVIVORS: A couples-based approach should be considered in cancer survivorship programs so that outcomes can mutually benefit both partners. TRIAL REGISTRATION: ClinicalTrials.gov NCT00954044.

GATA4 and GATA6 Knockdown During Luteinization Inhibits Progesterone Production and Gonadotropin Responsiveness in the Corpus Luteum of Female Mice.

The surge of luteinizing hormone triggers the genomic reprogramming, cell differentiation, and tissue remodeling of the ovulated follicle, leading to the formation of the corpus luteum. During this process, called luteinization, follicular granulosa cells begin expressing a new set of genes that allow the resulting luteal cells to survive in a vastly different hormonal environment and to produce the extremely high amounts of progesterone (P4) needed to sustain pregnancy. To better understand the molecular mechanisms involved in the regulation of luteal P4 production in vivo, the transcription factors GATA4 and GATA6 were knocked down in the corpus luteum by crossing mice carrying Gata4 and Gata6 floxed genes with mice carrying Cre recombinase fused to the progesterone receptor. This receptor is expressed exclusively in granulosa cells after the luteinizing hormone surge, leading to recombination of floxed genes during follicle luteinization. The findings demonstrated that GATA4 and GATA6 are essential for female fertility, whereas targeting either factor alone causes subfertility. When compared to control mice, serum P4 levels and luteal expression of key steroidogenic genes were significantly lower in conditional knockdown mice. The results also showed that GATA4 and GATA6 are required for the expression of the receptors for prolactin and luteinizing hormone, the main luteotropic hormones in mice. The findings demonstrate that GATA4 and GATA6 are crucial regulators of luteal steroidogenesis and are required for the normal response of luteal cells to luteotropins.

Resistance Exercise Reduces Body Fat and Insulin During Androgen-Deprivation Therapy for Prostate Cancer.

PURPOSE/OBJECTIVES: To determine whether exercise could reduce biomarkers of cancer progression in prostate cancer survivors (PCSs) on androgen-deprivation therapy (ADT). DESIGN: Randomized, controlled trial. SETTING: Oregon Health and Science University School of Nursing. SAMPLE: 51 PCSs randomized to one year of resistance and impact training or a stretching control group. METHODS: The authors investigated changes in body composition and cancer-related biomarkers, and the influence of age and fat loss on changes in biomarkers. MAIN RESEARCH VARIABLES: Body composition (total fat, trunk fat, and lean mass), insulin, insulin-like growth factor-1, and sex hormone-binding globulin. FINDINGS: In the 36 PCSs with baseline and 12-month data, total fat (p = 0.02) and trunk fat (p = 0.06) mass decreased in the training group compared to gains in controls. Loss of total and trunk fat each mediated the relationship between groups and one-year change in insulin (p < 0.05). Age moderated the insulin response to exercise where insulin reductions were smaller with increasing age (p = 0.03). CONCLUSIONS: Resistance and impact exercise may reduce body fat among PCSs undergoing ADT, in turn exerting an insulin-lowering effect. IMPLICATIONS FOR NURSING: Nurses should counsel PCSs to exercise to reduce the risk of obesity and associated conditions, including cancer progression.

Incongruent perceptions of pain and physical function among families living with lung cancer.

PURPOSE: The purpose of the study was to examine the roles of concealment and communication in incongruence in perceptions of the lung cancer patient's physical function and pain severity. METHODS: Lung cancer patients and their family members (N = 108 family care dyads) rated the patient's physical function and pain severity. RESULTS: Multilevel modeling revealed that family members, on average, rated patient physical function significantly worse than patients; incongruence did not significantly differ from 0, on average, for pain severity. However, there was significant variability across family care dyads in how much incongruence existed within dyads. Controlling for depressive symptoms, family member role overload, family member physical function, the patients' cognitive impairment, relationship type, and stage of lung cancer, the patients' level of concealment was significantly associated with incongruence for both physical function and pain severity. Additionally, the family members' perceptions of communication problems in the dyad were significantly associated with incongruence for pain severity. Models accounted for 23 and 30 % of the incongruence in physical function and pain severity, respectively. CONCLUSIONS: Open communication and disclosure play important roles in the appraisal of symptoms within the lung cancer patient-family member dyad. These interpersonal factors may be promising targets for interventions to maximize patient and family member outcomes.

Resistance training reduces disability in prostate cancer survivors on androgen deprivation therapy: evidence from a randomized controlled trial.

OBJECTIVES: To investigate whether functionally based resistance exercise could improve strength, physical function, and disability among prostate cancer survivors (PCS) on androgen deprivation therapy (ADT); and to explore potential mediators of changes in outcomes from exercise. DESIGN: Randomized controlled trial. SETTING: Academic medical center. PARTICIPANTS: PCS (N=51; mean age, 70.2y) on ADT. INTERVENTION: PCS were randomized to moderate to vigorous intensity resistance training or stretching (placebo control) for 1 year. MAIN OUTCOME MEASURES: Maximal leg press and bench press strength, objective and self-reported physical function, and self-reported disability. Hierarchical linear modeling was used to test for significant group × time differences adjusting for covariates. RESULTS: Retention in the study was 84%, and median attendance to supervised classes was 84% in the resistance group. No study-related injuries occurred. Maximal leg strength (P=.032) and bench press strength (P=.027) were improved after 1 year of resistance training, whereas little change occurred from stretching. Self-reported physical function improved with resistance training, whereas decreases occurred from stretching (P=.016). Disability lessened more with resistance training than stretching (P=.018). One-year change in leg press strength mediated the relation between groups (resistance or stretching) and 1-year change in self-reported disability (P<.05). CONCLUSIONS: One year of resistance training improved muscle strength in androgen-deprived PCS. Strengthening muscles using functional movement patterns may be an important feature of exercise programs designed to improve perceptions of physical function and disability. Findings from this study contribute to the mounting evidence that exercise should become a routine part of clinical care in older men with advanced prostate cancer.

The role of patient pain and physical function on depressive symptoms in couples with lung cancer: a longitudinal dyadic analysis.

Drawing on the Developmental-Contextual Model (Berg & Upchurch, 2007), we examined the association between changes in patient physical health (pain severity and physical function) and changes in depressive symptoms in couples with lung cancer over a 12-month period. Patients and their spouses or partners (n = 77) were recruited using rapid case ascertainment and completed five waves of data collection (baseline, 3, 6, 9, and 12 months). Multilevel modeling was used to examine aggregate and time-varying effects of patient physical health on depressive symptoms. Results indicated that for patients and spouses, patient-rated mean pain severity was significantly positively associated with patient and spouse depressive symptoms and patient-rated mean physical function was significantly negatively associated with patient and spouse depressive symptoms. More importantly, increases in patient pain severity and declines in patient physical function were significantly associated with increases in patient depressive symptoms. However, only declines in patient physical function were significantly associated with increases in spouse depressive symptoms. These time-varying effects remained even when controlling for patient gender, patient age, patient stage of disease, spouse physical health, and relationship quality. Findings suggest the importance of examining the changing illness context on the couple as a unit and the complexity of interpersonal processes in the presence of a life-threatening illness.

Symptom incongruence trajectories in lung cancer dyads.

CONTEXT: There is little known about the pattern of change in patient-family member symptom incongruence across the lung cancer trajectory. OBJECTIVES: This study examined trajectories of patient-family member incongruence in perceptions of patient physical function, pain severity, fatigue, and dyspnea in lung cancer dyads and explored the association with family member grief after patient death. METHODS: Lung cancer patients and their family members providing care (n = 109 dyads) rated patient symptoms and physical function five times over 12 months. Symptom incongruence trajectories were analyzed using multilevel modeling. RESULTS: Patient-family member incongruence did not significantly change over time, on average, except in the case of patient physical function where incongruence significantly declined. There was significant variability around trajectories of incongruence for all symptoms except fatigue. Exploratory analysis on a subsample of 22 bereaved family members found that incongruence regarding patient fatigue was associated with family member grief two months after patient death. CONCLUSION: Findings suggest the importance of modeling symptom incongruence over time and taking a dyadic approach to the illness context to identify interventions that promote adjustment and quality of life for both patient and family member.

Measuring activity levels associated with rehabilitative care in hospitalized older adults.

Older adults often experience functional losses during hospitalization. Clinical care activities have been increasingly promoted as a way to help older hospitalized patients offset these losses and recover from acute illness. Little research exists to objectively measure clinical care activities. This study evaluated the utility and feasibility of using the Actiheart, a combined heart rate monitor and accelerometer, to measure heart rate and motion (activity counts) during five clinical care activities. Fifty-four adults, aged 65 and older, scheduled for surgery, participated in a simulation of activities. The Actiheart successfully measured motion and heart rate during each of the five activities. One-way repeated measures analyses of variance showed that the Actiheart discriminated significant differences within and across the five activities. This study supports the use of an activity monitor to quantify clinical care activities in research studies that can be translated into clinical care. However, the complexity associated with data collection and analysis using the Actiheart could limit its direct use in clinical research.

Skeletal response to resistance and impact training in prostate cancer survivors.

INTRODUCTION: Androgen deprivation therapy (ADT) is associated with significant bone loss and an increase in fracture risk among prostate cancer survivors (PCS). We investigated whether impact + resistance training could stop ADT-related declines in bone mineral density (BMD) among PCS on ADT. METHODS: We randomized 51 PCS (mean age, 70.2 yr) currently prescribed ADT to participate in 1 yr of impact + resistance training (Prevent Osteoporosis with Impact + Resistance (POWIR)) or in an exercise placebo program of stretching exercise (FLEX). Outcomes were proximal femur (total hip, femoral neck, and greater trochanter) and spine (L1-L4) BMD (g·cm) and bone turnover markers (serum osteocalcin (ng·mL) and urinary deoxypyrodinoline cross-links (nmol·mmol Cr)). RESULTS: Retention in the 1-yr study was 84% and median attendance to supervised classes was 84% in POWIR and 74% in FLEX. No study-related injuries were reported. There were no significant differences between groups for average L1-L4 BMD or for BMD at any hip site. When examining individual vertebrae, POWIR has a significant effect on preservation of BMD (-0.4%) at the L4 vertebrae compared with losses (-3.1%) in FLEX (P = 0.03). CONCLUSION: Impact + resistance training was a safe and acceptable form of exercise for older PCS on ADT. Among our limited sample, POWIR did not appear to have a clinically meaningful effect on hip or spine BMD, but some evidence of skeletal adaptation to resistance + impact training in an androgen-deprived state was apparent. Future studies need to be conducted on a larger sample of patients and should consider modifications to POWIR that could further enhance loading across the spine and at the hip to preserve BMD at these clinically relevant sites.

Musculoskeletal changes after 1 year of exercise in older breast cancer survivors.

INTRODUCTION: We have previously reported that 1 year of supervised resistance + impact training stopped bone loss and built muscle strength in older breast cancer survivors. The purpose of this study was to determine whether these benefits persisted 1 year after completion of the intervention. METHODS: Sixty-seven women from the original trial completed baseline and post-intervention body composition and muscle strength tests, and 44 women were available 1 year later for follow-up assessments. Bone mineral density (grams per square centimeter) of the hip and spine, muscle mass (kilograms), and fat mass (kilograms) were measured by dual-energy X-ray absorptiometry and maximal upper and lower body strength were measured by one-repetition maximum tests (kilograms). We compared between group changes across baseline (pre-intervention), 1 (post-intervention), and 2 years (1 year follow up) on study outcomes using repeated-measures analysis of covariance, adjusting for age. RESULTS: Significant group by time interactions were found for spine bone mineral density (BMD) (p < 0.01) and lower body muscle strength (p < 0.05), with a trend for upper body muscle strength (p = 0.05). Spine BMD remained stable across intervention and follow-up periods in exercisers compared with continuous losses in controls across 1- and 2-year periods. In contrast, lower body strength increased in exercisers across the intervention, but decreased to near-baseline levels during follow-up compared with no change over either time period in controls. CONCLUSIONS: Our data suggest that spine BMD can be preserved in older breast cancer survivors even after formal exercise training stops; however, muscle strength is not similarly maintained and may require continued participation in a supervised exercise program. IMPLICATIONS FOR CANCER SURVIVORS: Exercise programs aimed at improving musculoskeletal health should be considered in the long-term care plan for breast cancer survivors.

Patterns and predictors of symptom incongruence in older couples coping with prostate cancer.

PURPOSE: Prostate cancer survivors (PCSs) may experience persistent symptoms following treatment. If PCSs and spouses differ in their perceptions of symptoms, that incongruence may cause mismanagement of symptoms and reduced relationship quality. The purpose of this study was to examine symptom incongruence and identify the PCS and spouse characteristics associated with symptom incongruence in older couples coping with prostate cancer. METHODS: Participants in the study were older PCSs (>60 years) and their spouses (N=59 couples). Symptom incongruence was determined by comparing patient and spouse independent ratings of the severity of his cancer-related symptoms. Predictor variables included PCS age, time since diagnosis, PCS comorbidity, PCS and spouse depressive symptoms, and spouse caregiving strain. RESULTS: PCS and spouse ratings of his symptom severity and the amount of incongruence over his symptoms varied significantly across couples. Overall, couples rated a moderate level of PCS symptom severity, but PCSs and their spouses significantly differed in their perceptions of PCS symptom severity with spouses rating severity higher (t=-2.66, df=51, p<0.01). PCS younger age and high spouse caregiver strain accounted for 29 % of incongruence in perceptions of PCS symptom severity. CONCLUSIONS: This study is among the first to show that PCSs and spouses may perceive cancer-related persistent symptoms differently. Among this older sample, younger PCS age and spouse caregiver strain were associated with incongruence in symptoms perceptions in couples. These and other factors may inform future interventions aimed at preserving relationship quality in older couples who have experienced prostate cancer.

GATA4 and GATA6 silencing in ovarian granulosa cells affects levels of mRNAs involved in steroidogenesis, extracellular structure organization, IGF-I activity, and apoptosis.

Knockdown of the transcription factors GATA4 and GATA6 in granulosa cells (GCs) impairs folliculogenesis and induces infertility. To investigate the pathways and genes regulated by these factors, we performed microarray analyses on wild-type GCs or GCs lacking GATA4, GATA6, or GATA4/6 (G4(gcko), G6(gcko), and G4/6(gcko)) after in vivo treatment with equine chorionic gonadotropin. GATA4 deletion affected a greater number of genes than GATA6, which correlates with the subfertility observed in G4(gcko) mice and the normal reproductive function found in G6(gcko) animals. An even greater number of genes were affected by the deletion of both factors. Moreover, the expression of FSH receptor, LH receptor, inhibin α and ß, versican, pregnancy-associated plasma protein A, and the regulatory unit 2b of protein kinase A, which are known to be crucial for ovarian function, was greatly affected in double GATA4 and GATA6 knockouts when compared with single GATA-deficient animals. This suggests that GATA4 and GATA6 functionally compensate for each other in the regulation of key ovarian genes. Functional enrichment revealed that ovulation, growth, intracellular signaling, extracellular structure organization, gonadotropin and growth factor actions, and steroidogenesis were significantly regulated in G4/6(gcko) mice. The results of this analysis were confirmed using quantitative polymerase chain reaction, immunohistochemical, and biological assays. Treatment of GCs with cAMP/IGF-I, to bypass FSH and IGF-I signaling defects, revealed that most of the affected genes are direct targets of GATA4/6. The diversity of pathways affected by the knockdown of GATA underscores the important role of these factors in the regulation of GC function.

Frailty in older breast cancer survivors: age, prevalence, and associated factors.

PURPOSE/OBJECTIVES: To describe frailty and associated factors in breast cancer survivors (BCSs) and evaluate whether BCSs are frail at an earlier age than female participants from in two large epidemiological studies. DESIGN: Descriptive, cross-sectional. SETTING: School of Nursing at Oregon Health and Science University. SAMPLE: 216 BCSs aged 53-87 years who were a mean 5-7 years post-treatment and not currently participating in exercise. METHODS: Performance tests, clinical measures, and self-reported questionnaires provided baseline data on five criteria for frailty. MAIN RESEARCH VARIABLES: Frailty was defined as meeting three of the five criteria of the frailty phenotype: shrinking, exhaustion, low activity, slowness, and weakness. Data were compared to published data from women in the Cardiovascular Health Study (CHS) and Women's Health and Aging Study (WHAS). FINDINGS: Eighteen percent of BCSs aged 70-79 years were frail compared to 11% of women of the same age in the CHS and WHAS. Frailty was more common at a younger age in BCSs, and more BCSs were frail in all age groups compared to women in the CHS study until about age 80 years, when prevalence of frailty was similar in the two groups. Fifty percent of BCSs were classified as prefrail because they met one or two of the five frailty criteria. Higher body mass index increased the odds of frailty, and higher physical activity decreased the odds of frailty (odds ratio [OR] = 1.12, p = 0.003, and OR = 0.99, p = 0.000, respectively). CONCLUSIONS: Frailty and prefrailty may be common in BCSs and may occur at an earlier age than in adults without a history of breast cancer. IMPLICATIONS FOR NURSING: Nurses should be alert to prefrailty or frailty at a younger age in BCSs. Awareness and early intervention may delay or prevent frailty. KNOWLEDGE TRANSLATION: BCSs may be frail even when they are not yet considered older adults. Prefrailty in BCSs is important to recognize because it suggests impending frailty that could lead to reduced physical functioning or poor health. Prefrailty and frailty could be assessed in BCSs aged 50 years and older in a clinical setting using a few questions about weight, fatigue, and activity levels, in addition to simple tests of walking speed and grip strength, if warranted.

IGF-I signaling is essential for FSH stimulation of AKT and steroidogenic genes in granulosa cells.

FSH and IGF-I synergistically stimulate gonadal steroid production; conversely, silencing the FSH or the IGF-I genes leads to infertility and hypogonadism. To determine the molecular link between these hormones, we examined the signaling cross talk downstream of their receptors. In human and rodent granulosa cells (GCs), IGF-I potentiated the stimulatory effects of FSH and cAMP on the expression of steroidogenic genes. In contrast, inhibition of IGF-I receptor (IGF-IR) activity or expression using pharmacological, genetic, or biochemical approaches prevented the FSH- and cAMP-induced expression of steroidogenic genes and estradiol production. In vivo experiments demonstrated that IGF-IR inactivation reduces the stimulation of steroidogenic genes and follicle growth by gonadotropins. FSH or IGF-I alone stimulated protein kinase B (PKB), which is also known as AKT and in combination synergistically increased AKT phosphorylation. Remarkably, blocking IGF-IR expression or activity decreased AKT basal activity and abolished AKT activation by FSH. In GCs lacking IGF-IR activity, FSH stimulation of Cyp19 expression was rescued by overexpression of constitutively active AKT. Our findings demonstrate, for the first time, that in human, mouse, and rat GCs, the well-known stimulatory effect of FSH on Cyp19 and AKT depends on IGF-I and on the expression and activation of the IGF-IR.