The Impact of Hormones on the Nervous System

Introduction to hormones and the nervous system
Key hormones affecting the nervous system
Hormones and mood disorders
Cognitive function and hormones
Neurological disorders and hormonal imbalances
Hormones and behavioral changes
Current research and future directions
Conclusion 
References
Further reading


Hormones are a crucial part of the body's signaling system, and the controlled release of these compounds affects tissues around the body. Each of these hormones induces specific responses from these tissues, contributing to day-to-day living alongside situation-specific responses. It is unsurprising that dysfunction of this system can cause neurological issues; this aspect and more will be discussed in this article.

Image Credit: Magic mine/Shutterstock.com

Image Credit: Magic mine/Shutterstock.com

Introduction to hormones and the nervous system

Hormone is a term describing a group of compounds that act as messengers within the body. Each hormone has a unique 3D structure with a complementarily-shaped receptor. This complementary-shape model is typically described as a lock and key, whereby the hormone fits in the receptor as a key does to a lock, "opening it."

The chemical cascade that follows a hormone's binding to its receptor is unique to each of these pairs. This system allows hormones to be released from a gland to affect tissues all around the body, wherever the corresponding receptor is found, allowing for rapid systemic changes within the body.

An Overview Of Sex Hormones

Hormones are involved in many bodily functions, such as regulating temperature, metabolism, and sleep, to name but a few. 1–3 Understandably, then, there exists a connection between hormones and the nervous system.

The nervous system is the collection of neuronal tissue found within the body. This includes the central nervous system, which consists of the brain and spinal cord, and the peripheral nervous system, which includes the other neurons within the body, such as in the arms and legs.

Key hormones affecting the nervous system

There are a number of key hormones which modulate the nervous system. Cortisol is a classic when discussing hormones and the nervous system. Cortisol is associated with the stress response, a biological change that occurs within the body when faced with a threat.

In this case, the stress response leads to the secretion of cortisol, which allows the body to maintain an alert state. Cortisol also drives metabolic changes, increasing gluconeogenesis, a process through which the body can rapidly derive energy. 4

Both estrogen and progesterone have hormonal effects on brain function. Estrogen is thought to play a large role in cognitive function, which is described later in this article. 5 Progesterone, on the other hand, is thought to modulate aggression, with researchers using the increase in progesterone to explain the reduction of aggressive behavior in lactating mice. 6

Testosterone, a reproductive hormone typically associated with fertility, also affects brain function. Seen in greater concentrations in males than females, testosterone is strongly linked to spatial cognition. This relationship is most obviously seen in hypogonadal men, in which a study saw the hypogonadal group improve on a spatial cognition test at a much greater rate than the control group when treated with testosterone. 7

Set of chemical formulas of hormones and neurotransmitters in brain. Image Credit: Pikovit/Shutterstock.com

Set of chemical formulas of hormones and neurotransmitters in brain. Image Credit: Pikovit/Shutterstock.com

As suggested by their name, thyroid hormones are a pair of hormones (triiodothyronine (T3) and thyroxine (T4)) secreted from the thyroid gland. Thyroid hormones are key signaling molecules in neurodevelopment. A lack of T4 during pregnancy, for example, is associated with delayed or entirely arrested neurodevelopment, producing a variety of phenotypes. 8

Insulin is another hormone not typically associated with brain function; instead, it is normally thought of in the context of the storage of carbohydrates. Insulin affects the central nervous system in multiple ways, such as promoting the absorption of glucose in some neuronal tissues, as glucose is also present in the cerebrospinal fluid alongside blood plasma. 9

Insulin also promotes the secretion of luteinizing hormone-releasing hormone, which stimulates the release of luteinizing hormone, an important hormone in both male and female fertility. 9,10

Insulin is also thought to play a role in cognitive function, as seen in studies comparing diabetic patients vs control groups. Multiple studies corroborate poorer cognitive performance in diabetic groups. This effect seems most pronounced in verbal learning and memory skills. 9

Hormones and mood disorders

With the outlined effects hormones have on the brain, it is no surprise that there is a relationship between hormones and mental health. When hormonal regulation of the nervous system is varied, an individual's mental health may be impacted.

There are numerous hormones thought to contribute to conditions such as depression and anxiety. Androgen, especially in males, is thought to play a role; men suffering from an androgen deficiency in one study had high rates of both depression and anxiety (24% and 18%, respectively). 11

Corticotropin-releasing hormone (CRH) is another hormone implicated in both anxiety and depression. 12–15 CRH plays a role in the stress response in both the acute and recovery phases, leading scientists to speculate how this contributes to anxiety and depression. 16

Hormones are also connected to other mental disorders, such as bipolar disorder (BPD). In the euthymia state of BPD, both leptin and insulin are significantly elevated. 17 Manic and psychotic symptoms of BPD have also been shown to improve with treatment using exogenous test oestradiol (a steroid hormone). 18

Hormones and Mood Disorders - Jill E. Stocker, D.O.

Cognitive function and hormones

Cognitive function and hormones are closely linked, with hormonal regulation of the nervous system acting in both positive and negative ways. Cortisol has been shown to reversibly reduce memory performance in humans.

This is thought to occur as glucocorticoids affect a variety of biological processes within the hippocampus, such as synaptic plasticity. 19  As the hippocampus is thought to play a role in learning and memory, specifically the synaptic plasticity of this region, interruption of this process may affect memory faculties. 20,21

Estrogen also plays a role in cognitive function, impacting the brain's prefrontal cortex and hippocampus areas by inducing the creation of new synapses and dendritic spines. 5 In women undergoing the menopausal transition, deficits in both processing speed and the ability to concentrate are noted. 22

Neurological disorders and hormonal imbalances

In MS, hormones are thought to play a role within the lesions associated with the pathology. Within these lesions, there was a noticeable presence of both steroidogenic enzymes and receptor expression for said hormones. In the male cohort of this study, this increase of enzymes and receptors related to estrogen, whereas in the female cohort, this increase was associated with progesterone. 23

As current evidence suggests hormonal imbalances may play a role in the pathology of neurological disorders, hormonal therapies for such disorders are being explored. In MS, as macrophage activity is influenced by sex hormones, modulation of these hormones has been shown to attenuate aspects of the immune response.24,25

Sex steroids may also influence the remyelination of affected neurons in MS. This remyelination may occur through a variety of interactions, such as with insulin-like growth factor-1 or affecting cell types like astrocytes and oligodendrocytes. 25

Hormones and behavioral changes

With the described hormonal effects on brain function, hormones must play a role in behavior. Fluctuations of hormones may, therefore, cause behavioral changes. Puberty is an excellent example of how changes in hormones drive behavior changes.

During puberty, individuals undergo sexual maturation through physical changes. A surge in hormones drives these changes. Behavioral changes are also noted during puberty. Changes in behavior amongst boys, such as proactive aggression and risk-taking, may be due to testosterone, an increase in which is associated with both behaviors. 26,27

Current research and future directions

Recent studies have sought to explore how hormones (and their metabolites) may be used in treating neurodegenerative diseases. Allopregnanolone, a metabolite of progesterone, has been theorized to be beneficial in the treatment of Alzheimer's disease (AD) in slowing disease progression. 6

A recent study using rodent models of AD has shown allopregnanolone promotes neuronal and oligodendrocyte differentiation. Potentially signaling allopregnanolone could stimulate white and gray matter regeneration. 28

As highlighted earlier in this article, research should be careful to consider the impact hormones may have on mental health and neurological disorders and surrounding neuroendocrinology. Identifying hormonal imbalances that can be rectified through treatment may offer treatment for huge groups of individuals.

Conclusion

In conclusion, hormones are an essential part of the body's signaling mechanism, able to enact systemic changes. Hormonal regulation of the nervous system and its dysregulation affects both cognitive functions alongside mental health and neurological disorders.

Due to the tissue-wide effects hormones can exert, understanding how hormones impact individual cells, alongside the wider changes this causes, may allow for identifying the early stages of certain disorders.

 Alongside this, increased research into hormonal regulation of the nervous system may inform better treatment for such conditions. For patients with such conditions, continued innovative research is critical for improving their quality of life. Potentially offering both symptomatic and underlying cause treatment.

References

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2.        Jørgensen JOL, Krag M, Kanaley J, et al. Exercise, hormones, and body temperature. Regulation and action of GH during exercise. J Endocrinol Invest. 2003;26(9):838-842. doi:10.1007/BF03345233 https://pubmed.ncbi.nlm.nih.gov/14964435/

3.        Mong JA, Baker FC, Mahoney MM, et al. Sleep, rhythms, and the endocrine brain: Influence of sex and gonadal hormones. J Neurosci. 2011;31(45):16107-16116. doi:10.1523/JNEUROSCI.4175-11.2011 https://www.jneurosci.org/content/31/45/16107

4.        Thau L, Gandhi J, Sharma S. Physiology, Cortisol. Florida: StatPearls Publishing, Treasure Island (FL); 2023. https://www.ncbi.nlm.nih.gov/books/NBK538239/.

5.        Hara Y, Waters EM, McEwen BS, Morrison JH. Estrogen effects on cognitive and synaptic health over the lifecourse. Physiol Rev. 2015;95(3):785-807. doi:10.1152/physrev.00036.2014 https://pubmed.ncbi.nlm.nih.gov/26109339/

6.        Taraborrelli S. Physiology, production and action of progesterone. Acta Obstet Gynecol Scand. 2015;94(S161):8-16. doi:10.1111/aogs.12771 https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/aogs.12771

7.        Zitzmann M. Testosterone and the brain. In: Aging Male. Vol 9. ; 2006:195-199. doi:10.1080/13685530601040679 https://www.tandfonline.com/doi/full/10.1080/13685530601040679

8.        Williams GR. Neurodevelopmental and neurophysiological actions of thyroid hormone. J Neuroendocrinol. 2008;20(6):784-794. doi:10.1111/j.1365-2826.2008.01733.x https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2826.2008.01733.x

9.        Ghasemi R, Haeri A, Dargahi L, Mohamed Z, Ahmadiani A. Insulin in the brain: Sources, localization and functions. Mol Neurobiol. 2013;47(1):145-171. doi:10.1007/s12035-012-8339-9 https://pubmed.ncbi.nlm.nih.gov/22956272/

10.      D Nedresky, G Singh. Luteinizing Hormone. Florida: StatPearls Publishing, Treasure Island (FL); 2022.

11.      Bruining H, Swaab H, Kas M, van Engeland H. Psychiatric characteristics in a self-selected sample of boys with Klinefelter  syndrome. Pediatrics. 2009;123(5):e865-70. doi:10.1542/peds.2008-1954 https://pubmed.ncbi.nlm.nih.gov/19364768/

12.      Holsboer F, von Bardeleben U, Wiedemann K, Müller OA, Stalla GK. Serial assessment of corticotropin-releasing hormone response after dexamethasone  in depression. Implications for pathophysiology of DST nonsuppression. Biol Psychiatry. 1987;22(2):228-234. doi:10.1016/0006-3223(87)90237-x https://www.sciencedirect.com/science/article/abs/pii/000632238790237X

13.      Holsboer F, Von Bardeleben U, Gerken A, Stalla GK, Müller OA. Blunted corticotropin and normal cortisol response to human  corticotropin-releasing factor in depression. N Engl J Med. 1984;311(17):1127. doi:10.1056/NEJM198410253111718 https://www.nejm.org/doi/abs/10.1056/NEJM198410253111718

14.      Nemeroff CB, Owens MJ, Bissette G, Andorn AC, Stanley M. Reduced corticotropin releasing factor binding sites in the frontal cortex of  suicide victims. Arch Gen Psychiatry. 1988;45(6):577-579. doi:10.1001/archpsyc.1988.01800300075009 https://pubmed.ncbi.nlm.nih.gov/2837159/

15.      Nemeroff CB, Widerlöv E, Bissette G, et al. Elevated concentrations of CSF corticotropin-releasing factor-like  immunoreactivity in depressed patients. Science. 1984;226(4680):1342-1344. doi:10.1126/science.6334362 https://pubmed.ncbi.nlm.nih.gov/6334362/

16.      Reul JMHM, Holsboer F. On the role of corticotropin-releasing hormone receptors in anxiety and depression. Dialogues Clin Neurosci. 2002;4(1):31-46. doi:10.31887/dcns.2002.4.1/jreul https://www.tandfonline.com/doi/full/10.31887/DCNS.2002.4.1/jreul

17.      Misiak B, Kowalski K, Stańczykiewicz B, et al. Appetite-regulating hormones in bipolar disorder: A systematic review and meta-analysis. Front Neuroendocrinol. 2022;67. doi:10.1016/j.yfrne.2022.101013 https://pubmed.ncbi.nlm.nih.gov/35792198/

18.      Gogos A, Ney LJ, Seymour N, Van Rheenen TE, Felmingham KL. Sex differences in schizophrenia, bipolar disorder, and post-traumatic stress disorder: Are gonadal hormones the link? Br J Pharmacol. 2019;176(21):4119-4135. doi:10.1111/bph.14584 https://pubmed.ncbi.nlm.nih.gov/30658014/

19.      Foy MR, Stanton ME, Levine S, Thompson RF. Behavioral stress impairs long-term potentiation in rodent hippocampus. Behav Neural Biol. 1987;48(1):138-149. doi:https://doi.org/10.1016/S0163-1047(87)90664-9 https://www.sciencedirect.com/science/article/abs/pii/S0163104787906649

20.      Squire LR. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev. 1992;99.2:195.

21.      Wilson M, Tonegawa S. Synaptic plasticity, place cells and spatial memory: study with second generation knockouts. Trends Neurosci. 1997;20(3):102-106. doi:10.1016/S0166-2236(96)01023-5 https://www.sciencedirect.com/science/article/abs/pii/S0166223696010235

22.      Kok HS, Kuh D, Cooper R, et al. Cognitive function across the life course and the menopausal transition in a British birth cohort. Menopause. 2006;13(1). https://journals.lww.com/menopausejournal/fulltext/2006/13010/cognitive_function_across_the_life_course_and_the.7.aspx.

23.      Luchetti S, Van Eden CG, Schuurman K, Van Strien ME, Swaab DF, Huitinga I. Gender differences in multiple sclerosis: Induction of estrogen signaling in male and progesterone signaling in female lesions. J Neuropathol Exp Neurol. 2014;73(2):123-135. doi:10.1097/NEN.0000000000000037 https://academic.oup.com/jnen/article/73/2/123/2917623

24.      Miller L, Hunt JS. Sex steroid hormones and macrophage function. Life Sci. 1996;59(1):1-14. doi:https://doi.org/10.1016/0024-3205(96)00122-1 https://www.sciencedirect.com/science/article/abs/pii/0024320596001221

25.      Kipp M, Beyer C. Impact of sex steroids on neuroinflammatory processes and experimental multiple  sclerosis. Front Neuroendocrinol. 2009;30(2):188-200. doi:10.1016/j.yfrne.2009.04.004 https://pubmed.ncbi.nlm.nih.gov/19393685/

26.      Vermeersch H, T’Sjoen G, Kaufman J-M, Vincke J. The role of testosterone in aggressive and non-aggressive risk-taking in adolescent boys. Horm Behav. 2008;53(3):463-471. doi:https://doi.org/10.1016/j.yhbeh.2007.11.021 https://www.sciencedirect.com/science/article/abs/pii/S0018506X07002899

27.      van Bokhoven I, van Goozen SHM, van Engeland H, et al. Salivary testosterone and aggression, delinquency, and social dominance in a population-based longitudinal study of adolescent males. Horm Behav. 2006;50(1):118-125. doi:10.1016/j.yhbeh.2006.02.002 https://pubmed.ncbi.nlm.nih.gov/16631757/

28.      Chen S, Wang T, Yao J, Brinton RD. Allopregnanolone Promotes Neuronal and Oligodendrocyte Differentiation In Vitro and In Vivo: Therapeutic Implication for Alzheimer's Disease. Neurotherapeutics. 2020;17(4):1813-1824. doi:10.1007/s13311-020-00874-x https://pubmed.ncbi.nlm.nih.gov/32632771/

Further Reading

 

Last Updated: Jul 8, 2024

Matthew Adams

Written by

Matthew Adams

Matt is a postgraduate in Clinical Neuroscience.  While studying for a BSc in Neuroscience at Keele University, Matt developed an interest in the clinical aspect of sciences, which led to his enrolment in the Clinical Neuroscience MSc program at UCL.  During his time at UCL, Matt collaborated with staff at the Institute of Neurology. Providing genetic diagnosis for patients with rare neuromuscular disorders within the UK and India. This project identified new cases of PYROD1-associated myopathies, including both expanding the currently understood phenotype of patients and identifying a new splice-altering variant. Through this research, Matt developed a strong passion for genomics in rare diseases, especially neurodevelopment and neuromuscular conditions. Matt is interested in improving the diagnosis of these rare diseases alongside exploring potential therapeutics

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