Fecal glucocorticoid metabolite and T3 profiles of orphaned elephants differ from non-orphaned elephants in Zambia

Many times, members have mentioned issues in their early lives. In this paper, these are referred to as early-life adverse events (ELAEs).

I note that diogenes several times referred to issues such as stress in early life as being causative, or at least contributory, to thyroid issues.

It is, in my view, entirely reasonable to look for links between elephants and humans. We have a lot in common. 

Fecal glucocorticoid metabolite and T3 profiles of orphaned elephants differ from non-orphaned elephants in Zambia

Daniella E Chusyd  1 , Janine L Brown  2 , Steve Paris  2 , Nicole Boisseau  2 , Webster Mwaanga  3 , Moses Kasongo  3 , Lisa Olivier  3 , Stephanie L Dickinson  4 , Bailey Ortyl  4 , Tessa Steiniche  1 , Steven N Austad  5   6 , David B Allison  4   5 , Michael D Wasserman  7

    PMID: 40196305 PMCID: PMC11974515 DOI: 10.7717/peerj.19122

Abstract

Background: 

Elephants provide valuable insight into how early-life adverse events (ELAEs) associate with animal health and welfare because they can live to advanced ages, display extensive cognitive and memory capabilities, and rely heavily on social bonds. Although it is known that African savanna elephants that experienced ELAEs, such as being orphaned due to human activities, have altered behavioral outcomes, little is known regarding the physiological consequences associated with those stressors.

Methods: 

We compared fecal glucocorticoid (fGCM) and thyroid (fT3) metabolites as well as body condition scores (BCS) in rescued and rehabilitated orphaned (early-dry season: n = 20; late-dry season: n = 21 elephants) African savanna elephants in Kafue National Park, Zambia to age- and sex-matched wild non-orphaned controls groups (early-dry season: n = 57; late-dry season: n = 22 elephants) during the early- (May/June) and late- (September/October) dry seasons, respectively. Age and sex were known for orphans. For non-orphan controls, age was estimated based on dung diameter, and sex was determined based on external genitalia. Hormone concentrations were compared between groups by age class to account for developmental and nutritional transitions experienced in early life. Given that environmental stressors (e.g., availability of food and water sources) change over the course of the dry season, early- and late-dry seasons were separated in the analyses.

Results: 

fGCM concentrations were higher in orphans at younger ages than non-orphaned controls of any age. This may be due to the younger orphans being temporally closer to the traumatic event and thus not having had sufficient time to establish meaningful social bonds that could buffer the negative outcomes associated with ELAEs. Alternatively, orphans could have acclimated to living under human care, resulting in fGCM concentrations that were not different from wild controls at older ages. Orphans also had significantly higher mean fT3 concentrations than non-orphans, suggesting increased caloric intake during rehabilitation. There was no difference in BCS between orphan and non-orphan elephants at any age or time period, possibly reflecting the limitations associated with BCS assessments in younger elephants.

Conclusions: 

Together, these results provide insight into possible physiological responses underlying ELAEs and/or living under human care, including alterations in fGCM and fT3 concentrations, particularly in younger orphans. While these hormonal changes suggest a physiological response to trauma, the support of social bonds and acclimation to human care may mitigate long-term stress effects, highlighting the critical role of social integration in elephant rehabilitation and conservation efforts.

Keywords: African savanna elephants; Early life adversity; Stress; Thyroid hormone. 

https://pubmed.ncbi.nlm.nih.gov/40196305/

Open access here:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11974515/

Mechanism of triiodothyronine alleviating acute alcoholic liver injury and delaying alcoholic liver fibrosis progression

Much of the time we hear lots of negativity about T3 (liothyronine, triiodothyronine). We are told it will have horrendous effects on us - even in small doses.

While this study is on mice, it claims very significant benefits of T3 in relation to alcohol and liver disease.

Mechanism of triiodothyronine alleviating acute alcoholic liver injury and delaying alcoholic liver fibrosis progression

Renli Luo  1   2 , Sanqiang Li  1   2 , Mengli Yang  1   2 , Junfei Wu  1   2 , Jiayang Feng  1   2 , Yue Sun  1   2 , Yadi Zhao  1   2 , Longfei Mao  1

    PMID: 40170552 DOI: 10.1177/09603271251332505

Abstract

Introduction

Alcoholic liver disease poses a severe threat to human health. The thyroid hormone Triiodothyronine (T3) is closely related to liver metabolism. This study investigated the effect and mechanism of T3 in alcoholic liver injury.

Methods

Acute alcoholic liver injury model was established in mice by alcohol administration. Alcoholic liver fibrosis models were established in vivo and in vitro using hepatic stellate cells (HSC)-T6 cells and mice. The role and regulatory mechanism of T3 in the occurrence and progression of alcoholic acute liver injury and fibrosis were analyzed by evaluating key factors involved in cell proliferation and apoptosis, inflammatory response, oxidative stress, and autophagy using histopathological staining.

Results

The results showed that T3 at low and medium concentrations reduced inflammation and oxidative damage in acute alcoholic liver injury and inhibited HSC activation and delayed the onset and progression of alcoholic liver fibrosis in mice. T3 inhibited the PI3K/AKT and NF-κB signal pathway, increased Nrf2 expression levels, and restored liver autophagy. However, high T3 concentrations had the opposite effect.

Discussion

Optimal T3 concentrations protects the liver from alcoholic liver injury by inhibiting inflammatory response and oxidative stress injury and by restoring hepatocyte proliferation, apoptosis, and autophagy.

Keywords: alcoholic liver disease; autophagy; hepatic stellate cells; liver fibrosis; oxidative stress; thyroid hormone.

Open access:

https://pubmed.ncbi.nlm.nih.gov/40170552/

https://doi.org/10.1177/09603271251332505

https://journals.sagepub.com/doi/10.1177/09603271251332505

What happens to T3?

If you are familiar with thyroid hormones, you will probably be aware that the interaction of the T3 hormone (tri-iodo-thyronine) with the T3 receptor is how it has its effects on cells.

We need enough T3 - much of which will be transported into our cells from the bloodstream. (Some might be formed by de-iodinating T4 within cells. But I'm desperately trying to simplify this to the extreme!)

The diagram below illustrates T3 (whether supplied to the cell as T3 or converted within the cell) to the T3 receptors in the nucleus. 

We often see descriptions of T3 (and many other substances) reaching their receptors as if a key is being put into a lock. And that makes it very clear that only the specific substance can actually properly activate the receptor. Other substances could potentially block a receptor, or act rather like the the proper substance - but often with less (or more) stimulation of the receptor.

For example:

• Blocking TSH-receptor antibodies prevent the usual TSH stimulating the thyroid gland to produce and release thyroid hormone.
• Stimulating TSH-receptor antibodies act more powerfully than the usual TSH thus stimulating the thyroid gland to produce and release excess thyroid hormone. Which is the fundamental issue in Graves disease.

But what is almost never discussed is what happens to the T3 when it has locked into the receptor. How long does it remain there? What eventually makes the receptor releasee it? Why doesn't that T3 molecule immediately re-attach to that same receptor? Or, if that receptor has become exhausted, why does it not attach to another T3 receptor?

Or does the T3 attach to several T3 receptors in succession?

I find it difficult to see how to combine the processes that would appear obvious with the extremely tight requirement for T3.

If one T3 molecule can attach to multiple receptors, what controls the total number?

Does the T3 molecule released by the T3 receptor get expelled from the cell?

Does the T3 molecule get degraded in some way? Or converted into T2? In which case we need to go through the same questions regarding T2 and T2 receptors!