Teaching Trans-Centric Curricular Content Using Modified Jigsaw.

Introduction: Transgender (trans) individuals have unique medical needs and difficulty accessing quality health care, exacerbated by inadequate provider knowledge. Incorporation of trans health care into medical school curricula has increased recently to address this gap. Jigsaw activities emphasize positive interdependence through structured cooperative learning, resulting in increased interest and self-confidence. We implemented a voluntary 2-hour modified jigsaw exercise on trans health care with changes designed to optimize the structure for medical students. Methods: The session was implemented both in person and virtually over 2 years with preclerkship medical students at the end of their endocrine/reproduction physiology course. The session featured a knowledge test with answer discussion followed by a clinical correlation-either a case discussion or video discussion. A pre- and posttest design compared students' knowledge, attitudes, and beliefs. Results: Eighty-nine students participated. Their initial attitudes and beliefs regarding trans health care were highly positive and remained elevated. Participants showed increases in knowledge and self-confidence discussing gender identity and clinical care postsession. All expressed interest in further training and felt the session enhanced their understanding of trans health and reproductive physiology. On 1-year follow-up, students showed decreased knowledge and self-confidence in discussing trans health; however, scores remained higher than presession. Student surveys suggested formal integration of more trans health education into the curriculum. Discussion: Medical students increased their knowledge and self-confidence regarding trans medicine and felt the modified jigsaw exercise was an effective teaching method. The results suggest that ongoing education is an important tool in optimizing trans health care.

Four Web-Based Interactive Endocrine Case Studies for Use in Undergraduate Medical Education.

INTRODUCTION: This resource is a collection of four case-based exercises intended to provide medical students with structured and focused opportunities to link basic science with clinical application. The cases are designed to help students self-evaluate their knowledge and develop a robust and well- integrated understanding of endocrine physiology and pathophysiology in the context of a representative range of endocrine disorders involving adrenal cortical, thyroid, and reproductive function. Although these cases were designed for, and used by, first-year students, they are also suitable for more advanced students. METHODS: Each case opens with a brief vignette containing a patient presentation and a history of present illness. The student first formulates a differential diagnosis and then sequentially narrows the differential by selecting from lists of diagnostic tests; correct answers with feedback are provided at each step. A diagnosis is ultimately required, and the student may be prompted to propose a treatment plan. RESULTS: End-of-course survey results from 128 first-year medical students suggest that the use of these interactive case studies was considered to be a worthwhile use of study time, and that knowledge gained in the correlate endocrine course was required to work through the cases. Students indicated that the levels of case and task complexity, along with feedback, were appropriate and helpful. DISCUSSION: These cases provide a resource for meeting the need for clinically relevant scenarios in the preclerkship years.

Skeletal muscle troponin as a novel biomarker to enhance assessment of the impact of strength training on fall prevention in the older adults.

BACKGROUND: Loss of muscle mass and strength (i.e., sarcopenia) in the older adults is a strong predictor of falls, with subsequent morbidity and inability to execute activities of daily living. Use of biomarkers may enhance assessment of effects of community-based exercise interventions aimed at improving muscle strength. OBJECTIVE: The aim of this study was to investigate the use of troponin as a newly proposed biomarker of skeletal muscle health when determining the outcomes of strength-training programs designed for community-dwelling adults over the age of 65 years. METHODS: Outcomes of two strength training programs ("Peer Exercise Program Promotes Independence" and "Stay Strong, Stay Healthy") were assessed using physical performance tests designed for senior fitness evaluation, grip strength, and changes in serum levels of skeletal muscle-specific troponin T (sTnT). RESULTS: Improvement in physical performance, including a significant increase in grip strength, was associated with a significant reduction in serum levels of sTnT. DISCUSSION: Findings from these studies suggest that, when "Peer Exercise Program Promotes Independence" and "Stay Strong, Stay Healthy" are implemented for at least 10 weeks, significant gains in strength are achieved. This strength improvement was associated with a reduction in serum levels of troponin, supporting the use of troponin as a novel biomarker of muscle health in the assessment of strength training programs for the older adults. Reduced sTnT after exercise intervention suggests that skeletal muscles become stronger and less susceptible to damage because of the exercise regimens.

Effect of the methoxychlor metabolite HPTE on the rat ovarian granulosa cell transcriptome in vitro.

Ovarian granulosa cells play a central role in steroidogenesis, which is critical for female reproduction. Follicle-stimulating hormone (FSH) promotes cyclic adenosine monophosphate (cAMP)-mediated signaling to regulate granulosa cell steroidogenesis. We have shown previously that 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) inhibits FSH- and dibutyryl cAMP-stimulated steroidogenesis and affects the messenger RNA levels of steroidogenic pathway enzymes in rat granulosa cells. However, HPTE showed a differential effect in FSH- and cAMP-stimulated cells in that HPTE more completely blocked FSH- when compared to cAMP-driven steroidogenesis. The objective of this study was to analyze the effects of HPTE on global gene expression profiles in untreated granulosa cells and those challenged with FSH or cAMP. Granulosa cells from immature rats were cultured with 0, 1, 5, or 10 microM HPTE in the presence or absence of either 3 ng FSH/ml or 1mM cAMP for 48 h. Total RNA was isolated for real-time quantitative PCR and microarray analysis using the GeneChip Rat Genome 230 2.0 and ArrayAssist Microarray Suite. An investigation of changes in gene expression across all HPTE treatments showed that HPTE altered more genes in FSH- (approximately 670 genes) than in cAMP-stimulated cells (approximately 366 genes). Analysis confirmed that HPTE more effectively inhibited FSH- than cAMP-induced steroid pathway gene expression and steroidogenesis. Furthermore, expression patterns of novel genes regulating signal transduction, transport, cell cycle, adhesion, differentiation, motility and growth, apoptosis, development, and metabolism were all altered by HPTE. This study further established that HPTE exerts differential effects within the granulosa cell steroidogenic pathway and revealed that these effects include broader changes in gene expression.

The hepatocyte growth factor system as a regulator of female and male gonadal function.

The hepatocyte growth factor (HGF) system comprises HGF, its receptor (the c-met tyrosine kinase), HGF activator (HGFA) protein, and HGFA inhibitor (HAI). The components of the HGF system have been identified in a plethora of tissues to include the ovary and testis. In its traditional context, the HGF system works via paracrine- and autocrine-mediated feedback in which HGF (of mesenchymal origin) binds and activates c-met (within epithelial cells); target cells then respond to HGF via any number of morphogenic and functional changes. The concomitant presence of HGFA and HAI suggests that HGF bioactivity can be locally modulated. A number of studies have collectively shown that the mammalian ovary and testis contain HGF, c-met, and HGFA; very little is currently known regarding HAI within the gonad. Within the ovary, HGF controls numerous key functions which collectively regulate the growth and differentiation of ovarian follicles; these include cell growth, steroidogenesis, and apoptosis within theca cells and/or granulosa cells. Comparatively, less is known about the function of HGF within the testicular Leydig and Sertoli cells, but evidence is emerging that HGF may regulate somatic cell function, including Leydig cell steroidogenesis. Changes in the cellular origin of HGF and c-met during fetal and postnatal testicular development suggest that HGF, in collaboration with other growth factors, may regulate important aspects of testicular cell morphogenesis and differentiation which enable male sexual viability. Likewise, experimental evidence showing that HGF can modulate many vital processes which enable ovarian follicle growth, differentiation, and function indicate the importance of HGF in female reproduction. This review presents what is currently known regarding the expression of the HGF system and its function within the ovary and testis.

Developmental exposure to environmental endocrine disruptors: consequences within the ovary and on female reproductive function.

Female reproductive function depends upon the exquisite control of ovarian steroidogenesis that enables folliculogenesis, ovulation, and pregnancy. These mechanisms are set during fetal and/or neonatal development and undergo phases of differentiation throughout pre- and post-pubescent life. Ovarian development and function are collectively regulated by a host of endogenous growth factors, cytokines, gonadotropins, and steroid hormones as well as exogenous factors such as nutrients and environmental agents. Endocrine disruptors represent one class of environmental agent that can impact female fertility by altering ovarian development and function, purportedly through estrogenic, anti-estrogenic, and/or anti-androgenic effects. This review discusses ovarian development and function and how these processes are affected by some of the known estrogenic and anti-androgenic endocrine disruptors. Recent information suggests not only that exposure to endocrine disruptors during the developmental period causes reproductive abnormalities in adult life but also that these abnormalities are transgenerational. This latter finding adds another level of importance for identifying and understanding the mechanisms of action of these agents.

Immunolocalization of the hepatocyte growth factor (HGF) system in the rat ovary and the anti-apoptotic effect of HGF in rat ovarian granulosa cells in vitro.

Hepatocyte growth factor (HGF) regulates granulosa cell (GC) steroidogenesis and suppresses apoptosis in non-ovarian cells. The hypothesis was thus developed that intraovarian HGF supports folliculogenesis by mediating steroidogenesis and suppressing apoptosis. To investigate the latter, the anti-apoptotic actions of HGF were tested in GCs and follicles isolated from immature rats. Results showed that HGF suppressed apoptosis in GC and follicle cultures as visualized using apoptosis indicator dye, YO-PRO-1. Immunohistochemistry was used to investigate the distribution of HGF, c-met, and HGF activator (HGFA) protein during folliculogenesis in equine chorionic gonadotropin (eCG)-primed rats. Immunoreactive HGF content was the greatest in GCs within preantral follicles. Following eCG, large antral follicles showed elevated HGF staining in theca and interstitial cells when compared with GCs. Intense c-met staining was observed in GCs within non-primed small preantral follicles; following eCG, the level of c-met was diminished in GCs, but increased within theca and interstitial cells. Theca, interstitium, and GCs in non-primed and primed ovaries contained HGFA. Following eCG, HGFA was more apparent in theca cells and the interstitium when compared to that in GCs within large antral follicles. The presence of HGF, c-met, and HGFA in preantral follicles would potentially enable the anti-apoptotic effects of HGF that were observed in vitro to occur in vivo. Advanced folliculogenesis led to a change in the cellular distribution of the HGF, c-met, and HGFA, suggesting that the ovarian HGF system is hormonally regulated in vivo.

The methoxychlor metabolite, 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane, inhibits steroidogenesis in rat ovarian granulosa cells in vitro.

The exquisitely balanced hormonal mechanisms that control female fertility can be affected by several internal and external factors including pathogens, genetic maladies, and environmental agents. In the latter group are natural and synthetic agents known as endocrine disruptors. One such compound, 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), is the predominant metabolite of the pesticide methoxychlor. The effects of HPTE on ovarian steroidogenesis have not been previously reported and were investigated in the present study. Granulosa cells harvested from immature rats were treated with follicle-stimulating hormone (FSH) or N(6),2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (db-cAMP) in the presence or absence of HPTE. After 48h, progesterone (P4) and estradiol-17beta (E2) concentrations were measured in the culture media. Steady-state levels of the mRNAs encoding steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), 3beta-hydroxysteroid dehydrogenase type 1 (3beta-HSD), and P450 aromatase (P450arom) were examined using real-time PCR. Both FSH- and db-cAMP-stimulated P(4) accumulation were impaired by HPTE. In contrast, FSH-, but not db-cAMP-stimulated, E2 content was suppressed by HPTE. The FSH-dependent increase in the abundance of P450scc, 3beta-HSD, and P450arom mRNAs was blocked by HPTE; however, StAR expression was not altered. Although db-cAMP-dependent P450arom was moderately reduced by HPTE, the levels of db-cAMP-dependent StAR, P450scc, and 3beta-HSD mRNAs were increased in the presence of HPTE. These data collectively show that HPTE can disrupt P4 and E2 production in granulosa cells, with implications for sites of action both preceding and following the generation of cAMP. The steroid-modulatory effects of HPTE in granulosa cells appear to involve the general suppression of the FSH-dependent expression of mRNAs encoding steroid pathway proteins, whereas the disparate effects of HPTE on cAMP-dependent mRNA content in this regard suggest a broader and more complex mechanism of action.

Effects of hepatocyte growth factor on cyclic nucleotide-dependent signaling and steroidogenesis in rat ovarian granulosa cells in vitro.

Hepatocyte growth factor (HGF) down-modulates FSH-dependent estradiol-17beta (E(2)) production in ovarian granulosa cells in vitro. The mechanisms of action underlying the antiestrogenic effects of HGF are vague, although evidence indicates that HGF may affect cAMP signal transduction in rat granulosa cells. The present study investigated the effects of HGF on FSH-induced steroidogenesis in the presence and absence of insulin-like growth factor I (IGF-I), as well as the actions of HGF within cyclic nucleotide-dependent signal transduction cascades in granulosa cells. Immature rat granulosa cells were incubated with FSH, IGF-I, and HGF. HGF impaired the production of FSH-stimulated and FSH + IGF-I-stimulated E(2) synthesis, as well as FSH + IGF-I-dependent estrone production. Progesterone synthesis was not altered by HGF. HGF suppressed FSH-dependent cAMP content at 24 h, but not at 36 h; cGMP content was stimulated by HGF with and without FSH at 24 h. In the presence of the cyclic nucleotide phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX), FSH-dependent cAMP accumulation was not affected by HGF. The suppressive effect of HGF on FSH-dependent E(2) production was alleviated by IBMX, whereas the HGF-dependent block in FSH + IGF-I-supported E(2) production was not prevented by IBMX. The effects of HGF on cyclic nucleotide PDE activities were manifested in a time-dependent and hormone-dependent manner. FSH-induced cAMP PDE was suppressed by HGF at 24 h but not at 36 h, whereas FSH-dependent cGMP PDE was impaired at 36 h, but not at 24 h. HGF prevented the IGF-I-dependent reduction in FSH-stimulated cAMP-PDE activity at 24 and 36 h, and lowered FSH + IGF-I-stimulated cGMP-PDE activity at 36 h, concomitant with an HGF-dependent increase in cGMP content at 24 h. These data indicate that HGF affects cAMP-directed and cGMP-directed signaling pathways at multiple sites in granulosa cells. These HGF-dependent effects may provide insight for mechanisms of action whereby HGF reduces E(2) secretion by granulosa cells.