Characterization of human fetal adrenal function: Establishment of an ex vivo culture model that enables examination of steroidogenesis

Abstract

The difficulty of examining adrenal endocrine function during human embryonic/fetal life combined with the limited applicability of most animal models (higher primates excepted) has challenged research aiming to investigate human fetal adrenal (HFA) development and steroidogenic activity. Therefore, the exact endocrine function and regulation of HFAs remain largely unclear, although experiences from congenital adrenal disorders show that imbalanced adrenal steroidogenesis can have irreversible effects on the fetus. Thus, increased biological insight into HFA development and endocrine function may provide a basis to improve the clinical understanding of adrenal disorders.

The aim of this thesis was to establish a long-term culture model that can contribute to a more detailed understanding of normal HFA development and the consequences of imbalanced steroidogenic activity. To accomplish this, three specific aims have been addressed: 1) Characterize the expression pattern of steroidogenic enzyme and determine HFA tissue concentrations of steroid hormones. 2) Establish a novel HFA ex vivo culture model that allows examination of basal and manipulated steroidogenesis. 3) Examine the effects of selected steroidogenic inhibitors on fetal adrenal tissue cultured ex vivo under basal and ACTH stim lated conditions.

Place of employment

PhD author

Cecilie Melau, cand.scient.

Date and place of defense

28th May 2021, Rigshospitalet, Auditorium 2, Copenhagen, Denmark.

Supervisors

Primary supervisor: Senior scientist Anne Jørgensen, MSc, PhD
Principal supervisor: Professor Anders Juul, MD, PhD, DMSc

Links
JCEM
JCEM
BMC Medicine




Responsible editor