General

Our research in general...

The research of the Laboratory of Comparative Endocrinology is focussed on vertebrate development and growth. Specifically, we study development and growth from an endocrinological perspective, identifying the underlying hormonal interactions. Emphasis is on the hormones of the thyroidal axis and their interactions with hormones of other endocrine axes such as the adrenal axis and the somatotropic or growth hormone axis. Our present research is centered around two topics: (i) the role of thyroid hormones in brain development, and (ii) the role of thyroid hormones and interacting hormones in the early phases of embryonic development. Hormonal actions are studied at the molecular level (DNA, RNA, protein), at the level of tissues/organs level and at the level of the whole organism (see techniques and expertise). We compare the endocrine systems in representatives of all vertebrate classes, but the chicken and the zebrafish take up a central place in our research (see our page on animal models). Our comparative approach allows us to deduce general physiological principles of growth and development in vertebrates. Moreover, our research provides a basis for applications in both medicine and animal production.

Some general aspect of the hypothalamo-hypophyseal thyroidal axis (HPT)

Environmental factors (light, temperature, stress) are translated into hormonal responses by the brain. Both stimulatory and inhibitory hormones are released by a ventral brain part, called the hypothalamus. These hypothalamic factors are transported to the pituitary gland, where they will bind specific membrane receptors on the target cells. This will stimulate or inhibit the synthesis and secretion of one or more hypophyseal hormones. In the rostral part of the pituitary, the pars distalis, several cell types can be distinguished: gonadotropes (producing FSH and/or LH), somatotropes (producing growth hormone), lactotropes (producing prolactin), thyrotropes (producing TSH), and corticotropes (producing ACTH). TSH, or thyrotropin, plays a central role in the HPT axis: it stimulates the thyroid gland to produce and secrete thyroid hormones. Thyroid hormones are crucial for a normal embryonic development in all vertebrates because of their effects on growth, cellular differentiation, and maturation of several organs, like the brain and the heart. Besides this developmental function, thyroid hormones also play an important role in the control of several metabolic processes throughout life.
Most of the effects of thyroid hormones are mediated by thyroid hormone receptors (TRs). TRs belong to the family of nuclear receptors, like those of the steroid hormones. Nuclear receptors function as hormone-activated transcription factors and thereby act by modulating gene expression. TRs bind to short, repeated sequences of DNA in the thyroid hormone-responsive genes, called thyroid hormone response elements (TREs). In contrast to steroid hormone receptors, TRs bind TREs in the absence of hormone, usually leading to transcriptional repression. Hormone binding is associated with a conformational change in the receptor causing it to function as a transcriptional activator. As in other vertebrates, two TR-genes have been identified in chicken, TRα and TRβ, giving rise to three different TR-transcripts (TRα, TRβ0 and TRβ2).
The two most important thyroid hormones (THs) are thyroxine or T4 and 3,5,3’-triiodothyronine or T3. While the latter has a higher affinity for the receptors, the thyroid secretes mainly T4 which is therefore considered to be a prohormone. T4 is activated by conversion to T3 by the removal of one iodine atom of the outer phenolic ring, a process that is carried out mainly in the peripheral tissues by enzymes called iodothyronine deiodinases. These enzymes are also responsible for the inactivation of T4 or T3 to either reverse T3 (rT3) or T2 respectively, by outer ring deiodination. Three different types of deiodinases have been identified: D1 with both activating and inactivating properties, D2 with only an activating function, and D3 which exclusively inactivates thyroid hormones. The final amount of bioactive T3 available within each cell is determined by the delicate interaction between these activating and inactivating enzymes, in collaboration with different thyroid hormone transporters which are located in the cell membrane and facilitate entrance and exit of T4, T3 and their metabolites.