SfE author summaries

 

To showcase the excellent work being published by Society of Endocrinology members in the Journal of Molecular Endocrinology, three recent authors have summarised their articles in four parts and described how they have benefited from Society of Endocrinology membership. Hear from Dr Sasha Howard, Dr Caroline Gorvin and Dr Nadia Islam.

 

Genetic Regulation in Pubertal Delay – Sasha Howard

What was the article?

This is a review summarising the recent discoveries in this field, highlighting techniques from genome wide association studies of the timing of puberty to next generation sequencing of familial cohorts, which have led to the identification of multiple new genetic pathways which modulate the timing of puberty.

Why was it of interest?

Disturbances of puberty encompass an important group of pathologies within the field of paediatric endocrinology, affecting 4% of adolescents. In addition, abnormal timing of pubertal development is associated with adverse health and psychosocial outcomes. This has importance not only for the individual, but also has a potential major impact on public health, especially in view of the secular trend towards an earlier age of puberty onset. Early puberty has for some time been associated with adverse health outcomes, and recent data from the UK Biobank study in both genders has demonstrated that pubertal delay also has profound impacts on health in later life.

What did you find?

There is remarkable genetic heterogeneity in the control of pubertal timing in the general population. Patients with mono- or digenic causes for their pubertal delay have now been identified in over 40 different genes and signalling pathways. Altogether, these genetic causes demonstrate that defects in GnRH neuronal development, GnRH secretion, upstream control or downstream action may all cause delay or disorder of pubertal timing.

What was its impact?

The considerable progress in understanding the mechanisms which control puberty over the last 10 years has been a success story of basic research in neuroendocrinology, but has also been translated into clinical practice. This has allowed a better understanding of the mechanisms of disordered pubertal development and, in an increasing number of cases, to enable diagnostic genetic testing and counselling.

Has being a member of the Society for Endocrinology benefitted you in your career?

Member benefits have included access to travel grants to attend scientific conferences, including the SfE annual BES meeting which is a lively and stimulating forum both for science and networking.

 

Molecular and clinical insights from studies of calcium-sensing receptor mutations – Caroline Gorvin

 

What was the article?

The article was a fairly comprehensive review of the molecular and clinical details of all mutations described in the calcium-sensing receptor (CaSR) to date. The CaSR is a G protein-coupled receptor that was discovered just over 25 years ago and has since been identified to play a major role in calcium homeostasis. Both gain- and loss-of-function mutations have been described in the receptor and cause disorders with opposite phenotype. By observing symptoms in patients with these genetic abnormalities and conducting cell-based studies of individual mutations, researchers have been able to uncover the mechanistic details of how the receptor signals and have led to the development of several drugs targeting the receptor.

Why was it of interest?

We are currently in an era in which more detailed genetic information is becoming available through large-scale sequencing projects (such as the UK BioBank) every day. While this provides an amazing resource, it also provides a somewhat overwhelming amount of information. I wanted to provide a comprehensive review of all the known CaSR mutations and provide information on their structural, clinical and cell signalling effects to help researchers make more informed decisions about whether newly identified CaSR variants are likely to have a pathogenic effect.

What did you find?

Using recently described crystal structures of the extracellular domain of the CaSR and a model of the CaSR transmembrane domain that I generated for the study, I mapped the positions of the disease-causing CaSR mutations and provided information on mutation 'hotspots'. Additionally, I provided updated clinical information on prevalence and symptoms observed in patients with mutations in the receptor.

What was its impact?

The information will hopefully be of use to clinicians, geneticists and researchers to help them make more informed predictions about whether genetic variants are likely to be disease-causing. Furthermore, I hope it provides a comprehensive picture of the current genetic landscape of the CaSR and demonstrates how much has been learned about the receptor in a relatively short time.

Has being a member of the Society for Endocrinology benefitted you in your career?

Being a member of the Society for Endocrinology has benefitted me in my career in several ways. Firstly, it has exposed me to fantastic networking opportunities with world-leading endocrine researchers by providing me with travel grants to attend several British Endocrine Society meetings, American Endocrine Society meetings and international GPCR meetings. Membership has also provided me with vital pilot funding through an Early Career Grant that allowed me to demonstrate early research independence. As I member I have also been able to contribute to the society by acting as the Basic Science lead for the Bone and Calcium Endocrine Network. Finally, the society has helped me enhance my research profile by awarding me with several prizes including the Basic Science Early Career Prize Lecture in 2017 and a recent Leadership and Development Award, as well as inviting me to speak at the annual BES meeting.

 

Steroids and microRNAs in assessment of ovarian tissue damage following cryopreservation - Nadia Islam

 

Why was it of interest?

Cryopreservation of ovarian cortical tissue is a novel approach to preserving fertility in women who are at risk of infertility, particularly in younger oncology patients. However, the effects of freeze-thawing are not fully understood, mainly due to the lack of suitable methods to assess tissue's survival after thawing. We investigated the possible interplay between steroid production and microRNAs’ expression pattern that could help in the assessment of tissue damage post freeze-thaw cycles.

What did you find?

Downregulation of microRNA-193b and microRNA-320A together with upregulation of microRNA-24 could have a synergistic role in cell apoptosis, and consequently leading to reduced oestradiol and progesterone production. As those microRNA markers paralleled oestradiol and progesterone concentration production by the follicular granulosa cells, it appears they are good indicators of apoptosis occurring within the granulosa compartment of follicles.

What was its impact?

There appears to be an interplay between these microRNAs, ovarian steroid production and cell damage, which can be further explored as novel non-invasive markers of cell damage following cryopreservation.

Has being a member of the Society for Endocrinology benefitted you in your career?

I am currently working as a specialty trainee in Obstetrics and Gynaecology at Sheffield Teaching Hospitals, also I am a final year PhD student at Nottingham University. I think being a member I get to know all the latest advancement and research done in the field of Reproductive medicine as well as molecular biology. In the long run, it will help me achieve my goals of becoming a successful clinician and researcher in reproductive Medicine.