BACKGROUND: Kisspeptin has recently been deemed the critical central regulatory factor for gonadotropin releasing hormone (GnRH) release. Through the control of GnRH release, kisspeptin is also responsible for the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), both downstream and regulated by GnRH. Kisspeptin is released from kisspeptin, neurokinin B, dynorphin A (KNDy) neurons within the hypothalamus’ arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). As the most prominent regulator of GnRH release, KNDy neurons directly influence the hypothalamic pituitary gonadal (HPG) axis. The HPG axis primarily regulates reproduction and can be inhibited by the presence of stress hormones, glucocorticoids (GCs), and activation of the hypothalamic pituitary adrenal cortex (HPA) axis. It was found that exposure to stress before and during puberty can lead to short-term pubertal delay and long-term physiological and behavioral alterations. It is known that a large portion of kisspeptin neurons contain glucocorticoid receptors (GR) which bind GCs. However, the exact pathway that allows HPA axis activation to inhibit the HPG axis is still unknown.
OBJECTIVE: The objective of this study is to understand how kisspeptin neurons mediate the relationship between the HPG and HPA axis and if the lack of GR from kisspeptin neurons alters pubertal development.
METHODS: A mouse model with the targeted deletion of GR from Kiss1 expressing neurons GRflox/flox; Kiss1-Cre (Kiss1GRKO) was compared to control (GRflox/flox) mice in phenotypic pubertal development studies. To determine if the removal of GR from Kiss1 expressing neurons affected pubertal development we began data recording of male and female mice phenotypes beginning on postnatal day (PND) twenty-one after weaning. We collected data assessing the body weight of the animal and age and body weight of preputial separation (PS), vaginal opening (VO), and first estrus, markers of pubertal development in mice.
RESULTS: The removal of GR from Kiss1 expressing neurons did not cause a significant difference in pubertal development. Male and female Kiss1GRKO and GRflox/flox mice did not have significantly different ages or body weights at PS or VO, nor was age and body weight significantly altered at first estrus.
CONCLUSION: The removal of GR and therefore the loss of the ability for Kiss1 expressing neurons to bind GCs does not appear to significantly alter pubertal development in male and female Kiss1GRKO mice. Further research and studies are necessary to determine if GR in kisspeptin neurons mediate the effects of stress on pubertal development.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/48201 |
| Date | 26 February 2024 |
| Creators | Fontes, Audrey Noelle |
| Contributors | Trinkaus-Randall, Vickery E., Pereira, Sidney A. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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