Epidermal growth factor increases cortisol production and type II 3 beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase expression in human adrenocortical carcinoma cells: evidence for a Stat5-dependent mechanism.

We tested the ability of epidermal growth factor (EGF) to regulate a key enzyme in the adrenal synthesis of glucocorticoids: human type II 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3 beta HSD). EGF treatment (25 ng/ml) of human adrenocortical carcinoma cells (H295R) resulted in a 5-fold increase in cortisol production and a corresponding 2-fold increase in 3 beta HSD mRNA. Experiments were performed to determine whether EGF is acting through a previously identified signal transducer and activator of transcription 5 (Stat5)-responsive element located from -110 to -118 in the human type II 3 beta HSD promoter. A Stat5 expression construct was cotransfected with a 3 beta HSD-chloramphenol acetyltransferase (CAT) reporter construct comprised of nucleotides -301-->+45 of the human type II 3 beta HSD promoter linked to the CAT reporter gene sequence. The addition of EGF at doses as low as 10 ng/ml resulted in an 11- to 15-fold increase in CAT activity. The introduction of 3-bp point mutations into critical nucleotides in the Stat5 response element obviated the EGF response. Either Stat5a or Stat5b isoforms induced CAT reporter expression upon treatment with EGF. These results demonstrate the ability of EGF to regulate the expression of a critical enzyme (3 beta HSD) in the production of cortisol and suggest a molecular mechanism by which this regulation occurs.

Insights into mentorship for endocrinologists.

CONTEXT: Effective mentorship is considered a prerequisite for success during medical training and an ensuing professional career in academic medicine. The Endocrine Society established sessions on mentorship at the Trainee Day during several annual meetings. These requests motivated a group of endocrinologists at the University of Virginia to assess prior literature on mentorship and collect opinions on the importance of the various characteristics of mentorship from endocrinologists, general faculty, and trainees. This information served as the basis for in-depth reflection and discussions on mentorship. OBJECTIVE: The goal was to identify and prioritize the quintessential elements involved in mentorship and to reach practical conclusions that would be beneficial to academic endocrinologists. COMMENTARY: A multigenerational mentorship tree emphasizes that successful mentors can influence generations of mentees and that this represents a multiplier effect. The authors propose that trainees who are informed about the most important characteristics of an effective mentor can make better choices of a mentor. On the other hand, mentors can best define expectations when mentees know what to expect from a mentor, based on key characteristics. CONCLUSIONS: Similarities and differences in expectation about mentorship can be leveraged for better communication between mentor and mentee and for the development of stage-appropriate educational curricula on academic mentorship.