Biochemistry Commons^™

Investigating The Role Of The Cholesterol Recognition/Interaction Amino-Acid Consensus Sequence In Follicle Stimulating Hormone Receptor Function And Structure, Tatyana Lynn

Honors Theses

Human infertility is a complex disorder that can often be attributed to a dysfunction of the endocrine system. Follicle-stimulating hormone (FSH) is one of many hormones that participate in a complex process in both women and men to regulate normal reproduction. The dysfunction of this hormone and its receptor are some of the many causes of infertility. FSH is secreted by the anterior pituitary and, in women, initiates a cascade of biological events that enable ovulation. FSH carries out its function by binding and activating specific receptors. The FSH receptor (FSHR) is a G protein-coupled receptor (GPCR) that is located …

Cortisol Receptor Sensitivity As A Risk Factor For Depression, Michela Michielli

Honors Theses

In 2020, the World Health Organization reported over 264 million people across the world were suffering from depression. Studies have demonstrated that one source of depression is a hormonal imbalance involved in the stress response. Cortisol is a stress hormone regulated by the Hypothalamic-Anterior-Pituitary (HPA) Axis. Its effects on the stress response and other metabolic activities in the body are exerted through the glucocorticoid and mineralocorticoid receptors (GR and MR respectively).

Our research has examined mutations known as single-nucleotide-polymorphisms (SNPs) relating to cortisol-receptor sensitivity and the behavior of cortisol in the body to investigate the link between cortisol activity and …

Lipid Raft Disruption Alters Human Follicle Stimulating Hormone Receptor Signaling, Rachel Judith Godek

Honors Theses

Over 6.7 million people struggle with infertility each year. Studying signaling by reproductive hormones in fertility can allow us to gain a better understanding of the signaling pathways that must function correctly for proper fertility. Some infertility is due to incorrect human follicle stimulating hormone receptor (hFSHR) function. When follicle stimulating hormone (FSH) binds to hFSHR this begins a signaling cascade where the end product is the maturation of sperm by Sertoli cells in men, and egg development and production of estrogen through stimulation of granulosa cells in women. It has been determined that hFSHR is localized to microdomains of …

Blocking The Entry Of Hiv Into Host Cells Through Co-Receptor Inhibition, Garyfallia Ralli

Honors Theses

The goal of our project is to synthesize a dual CXCR4/CCR5 co-receptor inhibitor to block the entry of HIV into host cells. In the early phase of the HIV-1 replication cycle, HIV-1 binds to host cells through the CD4 protein present on the host cell surface. To infect the cell, HIV-1 requires further interactions that promote fusion of the viral and cellular membranes. This can occur through binding to the chemokine co-receptors such as CXCR4 and CCR5. We are choosing dual inhibition since under selective pressure of a CCR5 antagonist, CXCR4-using strains have been shown to predominate. Through dual inhibition, …

Mutations In Caveolin Binding Motif Alter Human Follicle Stimulating Hormone Receptor Signaling, Katarina Zahedi

Honors Theses

Globally, there are about 48 million couples and 186 million individuals of reproductive age that are affected by infertility. Some cases of infertility in both men and women have been attributed to impaired follicle stimulating hormone (FSH) signaling. The lack of proper function of the cognate receptor for FSH (FSHR) could contribute to infertility since the biochemical signal generated by FSH binding to FSHR stimulates the production of a sperm-stabilizing protein in males and follicle maturation in females. It has been demonstrated that human FSHR (hFSHR) localizes to lipid rafts, which are rigid and detergent-resistant microdomains in the cell membrane. …

Analysis Of Caveolin-1 Expression And Interaction With Fshr In Lipid Raft Domains, Joseph Bott

Honors Theses

For thousands of women in the United States ovarian cysts, tumors, and hormonal imbalances contribute to reduced fertility and fecundity. In addition to these factors, many other unexplained physiological mechanisms may play a role in women’s reproductive health. Specifically, human follicle stimulating hormone (hFSH) binds to a G protein coupled receptor (GPCR) called human follicle stimulating hormone receptor (hFSHR). This interaction helps to regulate the reproductive system in both males and females indicating that it may be a key player to target in order to promote fertility. Previous work in our lab has demonstrated that hFSHR, like other GPCR, has …

Mutations In The Human Follicle Stimulating Hormone Receptor Caveolin Interaction Motif Cause Increased Basal Activation, Elizabeth Altman

Honors Theses

Over twelve percent of women aged fifteen to forty-five in America suffer from infertility and/or impaired fecundity and over seven million women have used infertility services, such as intrauterine insemination and in vitro fertilization. Some cases of infertility may be due to dysfunctional human follicle stimulating hormone (hFSH) signaling. hFSH plays a role in spermatogenesis in males, as well as follicle maturation and estrogen production in females. Problems with either hFSH or the hFSH receptor (hFSHR) decrease fertility in males and cause complete infertility in females. As part of the hypothalamic-pituitary-gonadal axis, hFSH is released from the pituitary gland and …

Caveolin Binding Motif Mutation Yields A Variance In Follicle Stimulating Hormone Receptor Signaling, Justin Fleischer

Honors Theses

The human follicle stimulating hormone receptor (hFSHR) is a glycoprotein hormone receptor belonging to the g protein-coupled receptor family. It is important in both male and female reproductive processes; defects in hFSHR can lead to infertility, delayed puberty, reduced muscle bulk, and osteoporosis. Work in other labs has shown that GPCRs can be localized to microdomains located within the cell membrane called lipid rafts. These regions are highly resistant to detergents because of the high concentration of sphingolipids and cholesterol. Also within these domains, an intracellular protein, caveolin, is present. Our lab has shown that hFSHR also localizes to lipid …

Quantification Of Hfshr Signaling To Determine Lipid Raft Residency, Gregory Geisel

Honors Theses

Human follicle stimulating hormone (hFSH) is a gonadotropin responsible for regulating reproductive systems by stimulation of Sertoli cells in males and granulosa cells in females. The hFSH receptor (hFSHR) is a seven transmembrane receptor that belongs to the G protein coupled receptor family. The receptor is functionally connected to a G protein on the inside of the cell. Once FSH activates its receptor, a cascade of signaling begins, resulting in the activation of adenylyl cyclase, which increases the intracellular levels of cAMP. In addition, hFSHR stimulation also activates the p44/42 MAP kinase. The spike in cAMP activates the enzyme protein …

Biological Activity Of A Set Of New Copper(Ii) Complexes: Toward Understanding Structure-Reactivity Correlations, Chelsea Aitken

Honors Theses

Cisplatin, carboplatin and oxaliplatin are all platinum-containing complexes that have been approved for use as chemotherapy drugs. The success of these complexes as well as their downfalls have sparked interest into alternative transition metal based compounds as potential chemotherapeutic agents. The use of platinum based complexes in cancer treatment has faced complications including cytotoxicity and drug resistance. The use of copper(II) as an alternative metal center is of specific interest because of bioavailability and elevated concentrations of this metal ion within tumor cells. Three copper complexes that utilize a nitrogen based ligand system, two of which contain a thiazole moiety …

Investigation Of The Mechanism Of Binding Of Perfluoroalkyl Acids With Human Serum Albumin Using An Improved Approach To Equilibrium Dialysis, Michael Morris

Honors Theses

Perfluoroalkyl acids (PFAAs) are used to produce many consumer products, but their bioaccumulative and toxic properties and their global persistence in the environment are major concerns. In particular, PFAAs have been shown to accumulate in the blood, liver, and kidneys of organisms. As such, it is important to elucidate the toxicokinetics of PFAAs by quantitatively and qualitatively characterizing the binding mechanism of PFAAs to human serum albumin (HSA). In this study, the binding of PFAAs to HSA are studied via a high-throughput equilibrium dialysis method that utilizes the 96-well Equilibrium Dialyzer coupled with sample quantitation using liquid chromatography tandem-mass spectrometry …

Mutagenesis Of The Caveolin Interaction Motif In Follicle Stimulating Hormone Receptor, Martin Cole

Honors Theses

Follicle Stimulating Hormone Receptor is a G-protein coupled receptor that localizes to rigid domains in the cell membrane known as caveolae. In the fourth transmembrane domain, there is a region of the receptor that contains a putative caveolin interaction motif (CIM), an alpha helix with 4 critical phenylalanine residues. These residues are critical to the localization of the receptor to caveolae. The goal of my research has been to mutate these phenylalanine residues to the amino acid leucine. Our hypothesis is that this conservative mutation will result in a mutant receptor that is no longer able to localize to the …