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Hyperthermic Conditioning Can Increase Release of Prolactin Which Helps Brain Function, Neurogenesis and Repair of Nerve Cell Damage

Prolactin (PRL), also known as luteotropic hormone or luteotropin, is a protein also known as a peptide hormone and is encoded by the PRL gene. Prolactin is best known in humans for its role in enabling female mammals to produce milk, but it is influential over a vast number of important functions (over 300 separate actions of PRL have been reported in various vertebrates. Prolactin is secreted from the pituitary gland in response to eating, mating, estrogen treatment, ovulation, and nursing. Prolactin is secreted in a pulsatile fashion in between these events. Prolactin also plays an essential role in metabolism, regulation of the immune system, and pancreatic development.

Prolactin also acts in a cytokine-like manner and as an important regulator of the immune system. It has important cell cycle related functions as a growth-, differentiating- and anti-apoptotic factor. As a growth factor, binding to cytokine like receptors, it also has profound influence on hematopoiesis, angiogenesis and is involved in the regulation of blood clotting through several pathways. The hormone acts in endocrine, autocrine, and paracrine manner through the prolactin receptor and a large number of cytokine receptors.

Pituitary prolactin secretion is regulated by endocrine neurons in the hypothalamus, the most important ones being the neurosecretory tuberoinfundibulum (TIDA) neurons of the arcuate nucleus, which secrete dopamine (aka Prolactin Inhibitory Hormone) to act on the D2 receptors of lactotrophs, causing inhibition of prolactin secretion. Thyrotropin-releasing factor (thyrotropin-releasing hormone) has a stimulatory effect on prolactin release, however Prl is the only adenohypophyseal hormone whose principal control is inhibitory.

Effects of Prolactin
Prolactin has a wide range of effects. It stimulates the mammary glands to produce milk (lactation): increased serum concentrations of prolactin during pregnancy cause enlargement of the mammary glands of the breasts and prepare for the production of milk. Prolactin provides the body with sexual gratification after sexual acts: The hormone counteracts the effect of dopamine, which is responsible for sexual arousal. This is thought to cause the sexual refractory period. The amount of prolactin can be an indicator for the amount of sexual satisfaction and relaxation. Unusually high amounts are suspected to be responsible for impotence and loss of libido.

Highly elevated levels of prolactin decrease the levels of sex hormones — estrogen in women and testosterone in men. The effects of mildly elevated levels of prolactin are much more variable, in women both substantial increase or decrease of estrogen levels may result.

Prolactin is sometimes classified as a gonadotropin although in humans it has only a weak luteotropic effect while the effect of suppressing classical gonadotropic hormones is more important. Prolactin within the normal reference ranges can act as a weak gonadotropin but at the same time suppresses GnRH secretion. The exact mechanism by which it inhibits GnRH is poorly understood although expression of prolactin receptors (PRL-R) have been demonstrated in rat’s hypothalmus, the same has not been observed in GnRH neurons. Physiologic levels of prolactin in males enhance luteinizing hormone-receptors in Leydig cells, resulting in testosterone secretion, which leads to spermatogenesis.

Prolactin also stimulates proliferation of oligodendrocyte precursor cells. These cells differentiate into oligodendrocytes, the cells responsible for the formation of myelin coatings on axons in the central nervous system.  Prolactin also has a number of other effects including contributing to pulmonary surfactant synthesis of the fetal lungs at the end of the pregnancy and immune tolerance of the fetus by the maternal organism during pregnancy.

Prolactin promotes neurogenesis in maternal and fetal brains.

Published studies have shown that prolactin can reduce the motivation to continue exercise, which is evident at fatigue during exercise in hot conditions  However, the measurement of central serotonergic and dopaminergic activity has practical limitations in humans, so the anterior pituitary hormone prolactin is often used as an indirect marker of central serotonergic and dopaminergic activity, since its release is regulated by the central serotonergic and dopaminergic systems. Serotonergic neurones in the dorsal raphe nucleus, located in the brainstem, stimulate the secretion of prolactin from serotonergic nerve terminals in the hypothalamus through activation of serotonergic receptors. Hypothalamic dopaminergic neurones that secrete dopamine into the pituitary portal vessels also tonically inhibit the secretion of prolactin. Significant increases in prolactin (which peak at the point of exhaustion) are evident during exercise in the heat that leads to an intolerable thermoregulatory strain. This suggests alterations in central serotonergic and dopaminergic activity, in response to the increased core temperature, that could contribute to the reduced motivation to continue exercise, and subsequently fatigue, in the heat. The prolactin responses at exhaustion were also significantly related to the core temperature responses at exhaustion in these studies, further supporting a link between thermal limits of athletic performance and prolactin levels.

Another study compared the prolactin and the cardiovascular responses at identical

core temperatures during an active (exercise) heating trial and a passive (water immersion) heating trial. The passive heating trial was used in this study to obtain similar core

temperatures to those achieved in an active (exercise) heat stress but with different cardiovascular responses owing to the absence of exercise. This design provided an insight

into the mechanisms of prolactin release and an indication of central serotonergic and dopaminergic activity relating to central fatigue during exercise-induced hyperthermia.

The specific hypothesis tested was that peripheral blood flow displacement, and an attendant drop in arterial blood pressure and therefore cerebral blood flow, stimulates the

release of prolactin during exercise in hot conditions. The study subjects sat and rested on the cycle ergometer for the same amount of time and under the same conditions as in the active exercise trial with no change in core temperature. In addition, subjects were also immersed

in the water bath at a thermoneutral temperature for the same duration as the passive heat stress and no change in core temperature was evident. In both of these control trials no change in prolactin was observed, indicating that being required to be seated on a cycle ergometer

or in a water bath, as in the present study, do not, per se,  cause changes in prolactin. In addition, the thermal discomfort ratings at the end of both forms of heating in the

present study indicated that the subjects terminated their trials at the point when thermal discomfort was almost maximal. In conclusion, active (exercise-induced) and passive

hyperthermia that invoked identical core temperatures yielded similar prolactin responses. This was despite different cardiovascular responses to the two forms of body heating. These results suggest that increases in core temperature, not alterations in peripheral blood flow and

blood pressure, provide the key stimulus for prolactin release, which may be a marker of central serotonergic and dopaminergic activity relating to central fatigue during exercise in hot conditions.

Although the present study did not include sequential blood sampling during the recovery period, the elevation of plasma prolactin has been shown to return to the baseline within 1 h after exercise. It is unknown how long the increased prolactin-receptor expression on B lymphocytes  continues. If the immunostimulatory function of prolactin and its half-life of

15–20 min are considered, exercise-induced elevation of prolactin is consistent with a promotion in immune cell function. Animal studies by Ortega et al. support this possible relationship. They demonstrated that acute aerobic exercise increased the plasma prolactin concentration as well as the phagocytic activity of macrophages in mice. Furthermore, previous studies with humans have demonstrated that there is an enhancement of antibody production or serum Ig concentrations in response to acute aerobic exercise. Although these investigators did not analyze prolactin, its presence is consistent with the elevations of serum immunoglobulin in response to acute exercise. Because of its immune-enhancing property, prolactin has been considered as a therapeutic agent for immune-deficient patients, including those undergoing bone marrow transplant and radiation/chemotherapy. In addition, hormone therapy may be useful for slowing a decline in the immune and other systems during aging. Although most animal studies have investigated prolactin in connection with surgical, chemical, and mechanical stress, the present study demonstrates a possible relationship between prolactin and human immune cells in response to exercise. Thus one of the positive effects of physical exercise may include an increase in endogenous prolactin especially for patients with a deficiency in the immune system. In summary, the present study demonstrated that acute aerobic exercise elevated plasma prolactin concentrations and the total number of circulating B lym-phocytes expressing prolactin receptor. In addition, there was an increase in total prolactin-receptor expression per B lymphocyte in response to exercise. Furthermore, B-cell prolactin-receptor expression was positively correlated with plasma prolactin concentrations. Thus this study supports the idea that physical exercise may enhance the interaction between human immune target cells and prolactin, a hormone capable of stimulating the immune function. The knowledge of exercise-induced immunoregulation may facilitate our total understanding of the intercommunication between endocrine and immune systems general, these studies were based on exogenous administration of prolactin, the use of surgical procedures, or the use of chemicals such as haloperidol to increase prolactin. In only one published study were the effects of prolactin elevation on prolactin-receptor expression by human leukocytes reported. This study indicated no significant difference in prolactin-receptor expression between hyperprolactinemic and normal subjects. However, chronic prolactin elevation at rest is likely different from an acute increase in prolactin through physical exercise by the healthy population in the present study. Moreover, Clodi et al., who examined cytokine production and NK cell activity of hyperprolactinemic patients with pituitary tumors, found that chronically elevated serum prolactin concentrations induced adaptation and abolished the acute immunostimulatory effects of prolactin. Therefore, acute prolactin elevation may in- crease prolactin-receptor expression by immune cells even though persistent acute prolactin elevation may not. In the present study, there was a significant positive correlation between plasma prolactin concentrations and total prolactin-receptor expression per B lymphocyte, although correlational analysis cannot establish causation. Another possible mechanism of exercise-induced prolactin-receptor expression may be mediated through cortisol, which is known to be immunosuppressive. High-intensity exercise is well known to increase cortisol concentrations.

APL (American Performance Labs) is a research group dedicated to the collection, analysis, and dissemination of published research and articles on the science of hyperthermia and the various applications, technologies and protocols for the use of hyperthermic conditioning.

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