Regulation of reproduction via tight control of gonadotropin hormone levels.

Mammalian reproduction is controlled by the hypothalamic-pituitary-gonadal axis. GnRH from the hypothalamus regulates synthesis and secretion of gonadotropins, LH and FSH, which then control steroidogenesis and gametogenesis. In females, serum LH and FSH levels exhibit rhythmic changes throughout the menstrual or estrous cycle that are correlated with pulse frequency of GnRH. Lack of gonadotropins leads to infertility or amenorrhea. Dysfunctions in the tightly controlled ratio due to levels slightly outside the normal range occur in a larger number of women and are correlated with polycystic ovaries and premature ovarian failure. Since the etiology of these disorders is largely unknown, studies in cell and mouse models may provide novel candidates for investigations in human population. Hence, understanding the mechanisms whereby GnRH regulates gonadotropin hormone levels will provide insight into the physiology and pathophysiology of the reproductive system. This review discusses recent advances in our understanding of GnRH regulation of gonadotropin synthesis

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice.

BackgroundThe mechanisms whereby neuroinflammation negatively affects neuronal function in the hypothalamus are not clear. Our previous study determined that obesity-mediated chronic inflammation elicits sex-specific impairment in reproductive function via reduction in spine density in gonadotropin-releasing hormone (GnRH) neurons. Neuroinflammation and subsequent decrease in GnRH neuron spine density was specific for male mice, while protection in females was independent of ovarian estrogens.MethodsTo examine if neuroinflammation-induced cytokines can directly regulate GnRH gene expression, herein we examined signaling pathways and mechanisms in males in vivo and in GnRH-expressing cell line, GT1-7.ResultsGnRH neurons express cytokine receptors, and chronic or acute neuroinflammation represses GnRH gene expression in vivo. Leukemia inhibitory factor (LIF) in particular represses GnRH expression in GT1-7 cells, while other cytokines do not. STAT3 and MAPK pathways are activated following LIF treatment, but only MAPK pathway, specifically p38α, is sufficient to repress the GnRH gene. LIF induces cFOS that represses the GnRH gene via the -1,793 site in the enhancer region. In vivo, following high-fat diet, cFOS is induced in GnRH neurons and neurons juxtaposed to the leaky blood brain barrier of the organum vasculosum of the lamina terminalis, but not in the neurons further away.ConclusionOur results indicate that the increase in LIF due to neuroinflammation induces cFOS and represses the GnRH gene. Therefore, in addition to synaptic changes in GnRH neurons, neuroinflammatory cytokines directly regulate gene expression and reproductive function, and the specificity for neuronal targets may stem from the proximity to the fenestrated capillaries

Examination of Participation and Occupation After Cancer

Cancer and treatments for cancer can have negative consequences on one’s ability to participate in life. Side effects of treatment, including pain, cognitive changes, and fatigue can last months to years after treatment. Community based support and services are emerging to fill a gap in care, specifically related to the psychosocial needs of the survivor. The purpose of this project was to provide information to Gilda’s Club Twin Cities (GCTC), a community based cancer support center, on the participation levels and quality of life (QOL) of their new members, with the secondary goal of collecting data on fatigue and cognitive issues. The study employed a cross sectional descriptive approach with self-report tools to examine the cancer population receiving services at a community based center. Standard, quantitative measures were used to describe participation in life activities, QOL, fatigue and cognition. Overall activity levels decreased 27% following a cancer diagnosis, with the subscale of high physical demand affected most. Participation in new activities was reported by 56%, with most of those activities falling into the instrumental category (doctor visits, resting). Social activities were identified as most important. QOL and fatigue mean scores were lower than the normative data for the general population and the cancer population in the United States. Opportunity and need exist in community based centers to provide effective programming related to participation levels, including fatigue management, role resumption, and the necessary performance skills to achieve personal participation goals. Occupational therapists should take the lead in supporting survivors in community based settings to achieve improved health, well being, and participation

First World War Memorials, Commemoration and Community in North East England, 1918-1939

ABSTRACT This thesis examines how local variations in economic, political, social, cultural and religious circumstances influenced First World War remembrance in the North East between the wars. It is divided into two parts. The first is concerned with the creation of every kind of memorial, from large county schemes to the smaller projects of villages and institutions. It investigates the people involved, the decisions they took, what they produced and the wider community’s response to their efforts. The second part considers commemoration - that is, the rituals and ceremonies which grew up around memorials, their public messages and private meanings, and how they began and evolved over time. It also considers the responses and attitudes of the veterans and the bereaved to public commemoration. The thesis finds that although there was a great deal of similarity in the way in which communities remembered, there were also differences. The differences can be located in the ways in which communities drew on their culture and traditions to ‘personalise’ remembrance and made it more meaningful, thus enabling them to return their loved ones ‘home’. However, from the little evidence available it is apparent that the bereaved had mixed feelings about remembrance, and it is uncertain how successful it was at assuaging grief. For the veterans, the experience of war and the difficulties they encountered on their return meant that they felt differently about remembrance and their priority was to reintegrate back into normal life