The neuroendocrine system encompasses the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-thyroid (HPT), and the hypothalamic-pituitary-gonadal (HPG) axes.
The hypothalamus, a small gland nestled in the brain, is the central regulator of the neuroendocrine system. It is a homeostatic regulator of hormones, metabolism, and age-related changes in our physiology.
The Neuroendocrine System
The HPA axis is a network of endocrine glands, neurons, hormones, and other signaling molecules that regulates the body’s stress response. It consists of three glands: The hypothalamus, the pituitary gland, and the adrenal glands. These three glands release a variety of hormones, including corticotropin-releasing hormone (CRH), cortisol, and DHEA, that orchestrate the stress response and impact longevity. (1, 2)
The HPT axis regulates the stress response as it relates to thyroid function. It comprises the hypothalamus, pituitary gland, and thyroid. (3) Insufficient thyroid hormone levels may contribute to fatigue, brain fog, and a lack of vitality with age, so maintaining proper HPT axis function is essential for optimizing longevity.
The HPG axis consists of the hypothalamus, pituitary gland, and gonadal glands, including the ovaries in females and testes in males. It controls the production of steroid hormones, including estrogen, testosterone, and DHEA, impacting sexual maturation and reproduction in adolescence and early adulthood.
Stress and Aging
The neuroendocrine system orchestrates the body’s response to stress. The stress response begins with the HPA axis, which is adept at responding to the types of acute stressors that our hunter-gatherer ancestors experienced in ancestral environments. However, this elegant system is far less proficient at responding to ongoing stressors, which account for most of the stress we face today.
Examples of ongoing stressors that significantly affect our HPA axis include:
- Perceived stress
- Circadian rhythm disruption
- Blood sugar dysregulation
- Out of control inflammatory response
Stress compromises HPA axis function which, in turn, impacts the HPT and HPG axes. For example, high levels of stress, blood sugar dysregulation, and an unhealthy inflammatory response compromise thyroid function and steroid hormone synthesis. (8, 9) Reductions in thyroid and steroid hormones perpetuate these issues creating a vicious cycle of dysfunction that can rapidly accelerate biological aging.
The activity of various longevity molecules, including NAD+ and sirtuins, also affects the neuroendocrine system. Neuron signaling in the hypothalamus is regulated by NAD+ availability; without sufficient NAD+, the hypothalamus cannot initiate the neuroendocrine cascade involved in adrenal, thyroid, and gonadal function. (10)
Support for Stress and Sex Hormones
At the level of the cell membrane, adaptogens and pregnenolone can support the aging neuroendocrine system. Adaptogens are botanicals that have been shown to reduce or counteract the adverse effects of stress, increase stamina, and optimize work capacity and mental performance without the downsides of conventional stimulants, such as caffeine. In other words, adaptogens help the body adapt to stress and increase resilience and vitality. (12) Interestingly, specific adaptogens, such as ginseng support an increase in the density of steroid hormone receptors in cell membranes, enabling the body’s cells to better respond to circulating levels of hormones. (13)
Pregnenolone is the hormone precursor to critical sex and stress hormones, including cortisol, DHEA, estrogen, progesterone, and testosterone. Pregnenolone helps maintain a normal balance between the body’s stress and sex hormones, supporting neuroendocrine balance and healthy aging.
Stress was previously thought to deplete pregnenolone through a process referred to as the “pregnenolone steal.” The pregnenolone steal concept proposes that when stress is high, the body shunts pregnenolone down a path that ultimately creates cortisol, leaving less pregnenolone available to create anti-inflammatory DHEA and vital sex hormones. However, we now understand that there is no single pool of pregnenolone available for all steroid hormone synthesis. Thus, demand for the production of cortisol in the adrenal cortex will not necessarily drain pregnenolone available for estrogen, progesterone, or testosterone production.
The downregulated production of sex hormones in response to stress is more a factor of processes such as feedback inhibition, receptor signaling, and gene expression that ultimately influence hormone production.