Comparative Endocrinology of Thyroid Function

Hormones secreted by the thyroid gland are of primary importance in the regulation of such fundamental physiological processes as growth, nutrient utilization, and reproduction. In my laboratory we examine the regulation of the secretion of thyroid hormones and their actions in poikilothermic vertebrates in order to understand the evolution of thyroid function. We are presently focusing on the regulation on thyroid hormone secretion and the mechanisms of iodine transport in commercially-important fish species such as the red drum (Sciaenops ocellatus), the channel catfish (Ictalurus punctatus), and even the zebrafish (Danio rerio).

We have discovered that blood thyroxine levels undergo robust daily cycles in the red drum, supporting a role for an endogenous clock in the central control of thyroid hormone production. Current studies are directed towards examining the regulation of thyroid hormone cycles and determining their physiological significance. I am also interested in the specific mechanisms through which nutrient intake influences thyroid hormone secretion and the manner in which thyroid hormone delivery to target tissues is influenced by circulatory factors unique to poikilotherms.  Thyroid hormone studies have led us to an examination of the mechanisms through which euryhaline fish obtain iodine from their environment.  We are currently examining the physiology of iodide transport in fish and hope to integrate it into a better understanding of the maintenance of thyroid homeostasis in variable marine environments.

A comparative perspective is always maintained in my research. Because of their position at the transition to endothermy, reptiles remain an interesting model for the examination of thyroid hormone action. For this reason, I also direct research on endocrine function in reptiles, such as sea turtles, desert tortoises, and alligators. From these animals we gain a broader perspective of the relationship between nutrient intake, temperature, and thyroid hormone production.

This research is aimed at providing new insights into the potentially ancient role of thyroid hormones in nutrient assimilation, as well as elucidating evolutionary trends in the regulation of thyroid function. These studies may serve identify ways in which the pituitary-thyroid axis may be manipulated to enhance aquaculture production or endangered species conservation.

1. Holloway, N, Riley, B, MacKenzie, DS. Expression of the sodium iodide symporter (NIS) in reproductive and neural tissues of teleost fish. Gen Comp Endocrinol. 2021;300 :113632. doi: 10.1016/j.ygcen.2020.113632. PubMed PMID:33002449 .
2. Jones, RA, Cohn, WB, Wilkes, AA, MacKenzie, DS. Negative feedback regulation of thyrotropin subunits and pituitary deiodinases in red drum, Sciaenops ocellatus. Gen Comp Endocrinol. 2017;240 :19-26. doi: 10.1016/j.ygcen.2016.09.003. PubMed PMID:27597549 .
3. Martinez, B, Soñanez-Organis, JG, Viscarra, JA, Jaques, JT, MacKenzie, DS, Crocker, DE et al.. Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups. Am J Physiol Regul Integr Comp Physiol. 2016;310 (6):R502-12. doi: 10.1152/ajpregu.00054.2015. PubMed PMID:26739649 PubMed Central PMC4867376.
4. Pasupuleti, S, Sule, N, Cohn, WB, MacKenzie, DS, Jayaraman, A, Manson, MD et al.. Chemotaxis of Escherichia coli to norepinephrine (NE) requires conversion of NE to 3,4-dihydroxymandelic acid. J Bacteriol. 2014;196 (23):3992-4000. doi: 10.1128/JB.02065-14. PubMed PMID:25182492 PubMed Central PMC4248876.
5. Jones, RA, Cohn, WB, Miller, TC, Jaques, JT, Mackenzie, DS. Cyclic mRNA expression of thyrotropin subunits and deiodinases in red drum, Sciaenops ocellatus. Gen Comp Endocrinol. 2013;194 :248-56. doi: 10.1016/j.ygcen.2013.09.017. PubMed PMID:24095808 .
6. Pohlenz, C, Buentello, A, Miller, T, Small, BC, MacKenzie, DS, Gatlin, DM 3rd et al.. Effects of dietary arginine on endocrine growth factors of channel catfish, Ictalurus punctatus. Comp Biochem Physiol A Mol Integr Physiol. 2013;166 (2):215-21. doi: 10.1016/j.cbpa.2013.06.016. PubMed PMID:23796823 .
7. Browning, ZS, Wilkes, AA, Mackenzie, DS, Patterson, RM, Lenox, MW. Using PET/CT imaging to characterize 18 F-fluorodeoxyglucose utilization in fish. J Fish Dis. 2013;36 (11):911-9. doi: 10.1111/jfd.12081. PubMed PMID:23488673 .
8. Miller, TC, Jaques, JT, Szkudlinski, MW, Mackenzie, DS. Thyrotropic activity of recombinant human glycoprotein hormone analogs and pituitary mammalian gonadotropins in goldfish (Carassius auratus): insights into the evolution of thyrotropin receptor specificity. Gen Comp Endocrinol. 2012;177 (1):70-5. doi: 10.1016/j.ygcen.2012.02.012. PubMed PMID:22387984 .
9. Scobell, SK, Mackenzie, DS. Reproductive endocrinology of Syngnathidae. J Fish Biol. 2011;78 (6):1662-80. doi: 10.1111/j.1095-8649.2011.02994.x. PubMed PMID:21651522 .
10. Cohn, WB, Jones, RA, Valverde, RA, Leiner, KA, MacKenzie, DS. Molecular cloning and regulation of mRNA expression of the thyrotropin β and glycoprotein hormone α subunits in red drum, Sciaenops ocellatus. Fish Physiol Biochem. 2010;36 (4):1277-90. doi: 10.1007/s10695-010-9408-5. PubMed PMID:20563882 .