Emily Fitz

The Role of FSH in Menopausal Osteoporosis and Subsequent Oral Disease


Osteoporosis is an age-related chronic disease in which osteoclasts degrade minerals of the bone faster than osteoblasts can replace them. In addition to increased risk of fracture, osteoporosis patients experience oral, dental and prosthodontic complications due to degradation of the alveolar and jaw bone. Elderly women are disproportionately impacted by this disease. One potential culprit for the gender-based disparity is the increased levels of follicle stimulating hormone (FSH) during menopause. An isoform of the FSH receptor can be found on osteoclasts; when FSH binds to this receptor, osteoclast activity and differentiation are increased. Murine monocytes were differentiated into osteoclasts using RANK ligand, and FSH dependent signaling was measured through Western Blotting. Proteins specific to the FSH-receptor pathway were detected in osteoclasts. A better understanding of the osteoclast FSH receptor could allow for pharmaceutical intervention to interrupt the pathway. Negative allosteric modulators (NAMs) that inhibit FSH signaling on granulosa cells could be used for inhibiting FSH signaling on osteoclasts.

Devon Hennel

Relationship Between Single Nucleotide Polymorphisms and Dysregulation of the HPA-axis in Predisposition to Depression

There is currently a gap between what is known about genetic susceptibility to depression and how the condition presents itself. It is known that individuals with diseases that cause too much or too little of the stress hormone cortisol, are typically diagnosed with depression. This led our lab and others to the hypothesis that genetic factors related to cortisol action may put someone at an increased risk for developing depression. We used allele specific PCR to study the frequency of single nucleotide polymorphisms in genes associated with the function of different components of the hypothalamic-pituitary-adrenocortical axis (HPA-axis) to determine if dysregulation is associated with increased risk. Additionally, saliva samples were taken to quantify cortisol levels. Thus far, we have found significant relationships between the glucocorticoid receptor (GR) SNPs rs41423247 and rs56149945 and scores on the Beck Depression Inventory. The GR SNP rs10052957 and the mineralocorticoid receptor SNP rs5522 showed significant relationships with the State and Trait Anxiety Inventory. We have also found that SNPs rs12086634 and rs5522 may be related to increased risk. In addition to these SNPs we are currently investigating over ten others. Understanding how these changes in the HPA axis relate to altered function may be an important part of determining how to better diagnose and treat depression. Through the use of genomic data, this research could provide the means to improve current treatments of depression and be the next step to personalized clinical care.

Alexandra Temple

Investigating Human Follicle Stimulating Hormone Receptor and its Partners Using the APEX Assay

Follicle stimulating hormone (FSH) and its receptor (FSHR) play important roles in reproduction and fertility in both men and women. Fertility problems arise when FSH, FSHR, or any downstream signaling components don’t function properly. FSHR is a G-protein coupled receptor (GPCR) found on the cell surface of granulosa cells in women and Sertoli cells in men. When activated by FSH, FSHR initiates a signaling cascade that can result in downstream results such as ovarian follicular development and estrogen production in women and sperm production in men. To better understand how the receptor functions, the interactions between FSHR and effector proteins involved in signaling must be identified and understood. We plan to study the interactions between FSHR and its effector proteins using the APEX Assay. This assay utilizes an engineered ascorbate peroxidase (APEX) which is attached to the C-terminus of FSHR. APEX modifies proteins using biotin phenol and hydrogen peroxide, which creates a biotin-radical, thus labeling proteins within a small radius of FSHR because of the short lived nature of the radical. Using mass spectrometry, the biotinylated proteins can be quantitatively analyzed to give a better understanding of the proteins associated with FSHR and the changes in the proteins over time after hormone treatment. Using HEK293 cells, we created a stable cell line expressing an FSHR-APEX construct. We are currently using the FSHR-APEX expressing cells in the APEX Assay to analyze the proteins that are involved in FSHR signaling. This research will give us a better insight as to what effector proteins interact with FSHR and how these interactions change following hormone stimulation. This will provide us with a better understanding as to how the receptor signals and initiates downstream signaling and how this might affect fertility in humans.