cortisol is the factor that is the first to be released in response to stress along the hpa-axis.
cortisol is the factor that is the first to be released in response to stress along the hpa-axis.
along the hpa-axis what is what factor is the first to be released in response to stress?
cortisol
additionally, external stress factors activate the hpa axis; increased corticotropin-releasing hormone (crh) secretion results in increased secretion of acth from the pituitary gland, and thus increased secretion of cortisol from the adrenal glands. crh, a regulator of the hpa and hpo axis, can be stimulated for release by the central nervous system in states of physical or mental stress that accompany the lifestyle factors contributing to amenorrhea. as a result, acth is released from the pituitary along with other pro-opiomelanocortin-related peptides such as beta-endorphin and b-lipotropic hormone. it is possible that increased levels of ghrelin in amenorrheic populations sensitizes the adrenal cortex to acth and is thereby associated with both hypothalamic crh release and the frequency of cortisol bursts. glucocorticosteroids are generally associated with inhibition of gnrh, adding strength to the stress-induced hypothesis of amenorrhea in some patients. by stimulating beta-endorphin, a hypothalamic and pituitary endogenous peptide, crh can indirectly alter lh function by acting upstream on gnrh. a combination of this factor, along with the direct inhibition of gnrh caused by elevated crh, may suggest a relationship between the incidence of stress- and exercise-related fha and opioidergic activity. fha patients have been found to have higher 24-hour mean plasma cortisol levels as well as increased cerebrospinal and urinary free cortisol levels; cortisol has negative effects on reproduction at the level of the hypothalamus, pituitary, and uterus. the increase in glucocorticoids inhibits the release of gnrh and gonadotropins and contributes to the pathophysiology of stress-related fha. it is currently unknown whether recovery from an or fha result in restoration of normal levels of cortisol, as there has not been a strong trend defined towards normalization associated with increases in bmi or changes in body composition. not insignificant is the necessity of prolonged hpa activation in the ability of this pathway to alter hypothalamic and/or pituitary control of ovulatory function, as mild fluctuations in these hormones do not appear to cause dysfunction. thus, reproductive function can be altered through psychological or physiological stress through the hpa axis due to the modulatory effects that this pathway has on the hpo axis: its activation, which can occur in states of low energy availability (lea) as an adaptive response to physical, nutritional, or extreme emotional stress, causes the release of crh; in turn, this leads to the inhibition of gnrh pulsatility directly at the level of the hypothalamus and therefore precludes multilevel inhibition of the hpo axis. the hypothalamic-pituitary-thyroid axis is also altered in fha; tsh levels are low-to-normal and there is an increase in reverse triiodothyronine and low level of triiodothyronine. relative energy expenditure (ree) is also closely linked to t, as is evidenced by a correlation between macronutrient intake, ree, and thyroid hormone levels. it has been found that an patients who regain weight can restore t and ree independent of changes in ffm.
functional hypothalamic amenorrhea
while the secretion of glucocorticoids in response to stressful stimuli is an adaptive response necessary for an organism to respond appropriately to a stressor, persistent secretion may be harmful. the endocannabinoid system has been implicated in the habituation of the hypothalamic-pituitary-adrenal axis (hpa axis) to repeated exposure to restraint stress. studies have demonstrated differential synthesis of anandamide and 2-ag during tonic stress. a decrease of anandamide was found along the axis that contributed to basal hypersecretion of corticosterone; in contrast, an increase of 2-ag was found in the amygdala after repeated stress, which was negatively correlated to magnitude of the corticosterone response. all effects were abolished by the cb antagonist am251, supporting the conclusion that these effects were cannabinoid-receptor dependent. these findings show that anandamide and 2-ag divergently regulate the hpa axis response to stress: while habituation of the stress-induced hpa axis via 2-ag prevents excessive secretion of glucocorticoids to non-threatening stimuli, the increase of basal corticosterone secretion resulting from decreased anandamide allows for a facilitated response of the hpa axis to novel stimuli.
endocannabinoid system