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Nathan Goodyear

The Androgen 5α-Dihydrotestosterone and Its Metabolite 5α-Androstan-3β, 17β-D... - 0 views

  • Sex steroid hormones are primarily responsible for sex difference in adult HPA function; androgens inhibit whereas estrogens enhance HPA axis activation after a stressor
  • the PVN contains relatively high levels of AR (Bingaman et al., 1994; Zhou et al., 1994) and ERβ (Alves et al., 1998; Hrabovszky et al., 1998; Somponpun and Sladek, 2003) but is essentially devoid of ERα
  • the nonaromatizable androgen DHT and the nonselective ER ligand E2 influence HPA reactivity by acting on neurons within or surrounding the PVN
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  • inhibitory action of DHT is detectable at both the level of hormone secretion as well as PVN c-fos mRNA expression
  • the inhibition can be mimicked by the DHT metabolite 3β-diol and by the subtype selective ERβ agonist DPN
  • E2 acts to enhance HPA reactivity
  • the ability of the ER antagonist tamoxifen, but not the AR antagonist flutamide, to block the inhibitory actions of DHT, speaks to the intracellular mechanism by which this inhibitory signal might be transduced.
    • Nathan Goodyear
       
      that is because the interaction with the DHT metabolite is not with the AR, but with the ER-beta.
  • the DHT metabolite 3β-diol and the ERβ-subtype-selective agonist DPN suppressed ACTH, corticosterone, and c-fos mRNA responses to restraint stress in a manner similar to DHT
  • metabolism of DHT to 3β-diol and subsequent binding to ERβ can be inhibitory to HPA reactivity, and this is one possible mechanism for the action of DHT.
  • Our data also suggest that E2 enhances the reactivity of the HPA axis to stress by acting on or near neurons of the PVN
  • the actions of E2 appear to be through an ERα-dependent mechanism
  • these studies suggest that ERβ, within the male hypothalamus, acts to inhibit the HPA axis and that the inhibitory effects of DHT may be, at least in part, via its intracellular conversion to 3β-diol and subsequent binding to ERβ
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    DHT metabolites: particularly 3beta-androstanediol inhibit HPA axis through ER-beta.
Nathan Goodyear

Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and... - 0 views

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    weight gain and obesity are associated with a dysfunctional HPA axis and low testosterone in men.  Reduction in weight will restore HPA axis function.
Nathan Goodyear

Inflammation and cortisol response in coronary artery disease: Annals of Medicine: Vol ... - 0 views

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    Inflammation disrupts HPA axis.  This is no surprise as we Know that inflammation can disrupt Testosterone in men and progesterone production in women.  This study suggests that this HPA axis disruption contributes to CAD.
Nathan Goodyear

Acupuncture blocks cold stress-induced increases in the hypothalamus-pituitary-adrenal ... - 0 views

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    acupuncture decreases HPA sympathetic drive.  Acupuncture calms the HPA axis and relieves stress.  Granted this is in a rat model.
Nathan Goodyear

Hypothalamic-Pituitary-Testicular Axis Disruptions in Older Men Are Differentially Link... - 0 views

  • 0.4–2% annual decline
  • the age trend in free T was more substantial (−1.3% per annum)
  • The core hormonal pattern with increasing age is suggestive of incipient primary testicular dysfunction with maintained total T and progressively blunted free T associated with higher LH.
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  • Obesity was associated with progressively lower total and free T independent of the simultaneous decrease in SHBG.
  • our data highlight the fact that LH was unchanged or even lower in older men in the face of lower T in obesity, suggesting that there may be a failure at the hypothalamic-pituitary level.
  • a change in BMI from nonobese to obese may be equivalent to a 15 yr fall in T.
  • This pattern supports the hypothesis that different underlying mechanisms influence the functions of the HPT axis: age predominantly affects testicular function, whereas obesity impairs hypothalamic/pituitary function.
  • the effects of aging on testicular function can be moderated by increased LH compensation for many decades
  • obesity impairs hypothalamic/pituitary function independent of age, arguably an adaptive response for which there should be no compensatory mechanism.
  • the concurrent but opposite (and separate) effects of obesity and age on SHBG
  • SHBG was negatively associated with increasing strata of obesity
  • Obesity is associated with insulin resistance (28), and the increased circulating insulin inhibits hepatic SHBG synthesis
  • the SHBG increase with age may be related to relative IGF-I deficiency (27), although this has not been directly proven.
  • Obesity is associated with peripheral and central insulin resistance (30) and proinflammatory cytokine production (TNFα and IL-6) from adipocytes (31) and central nervous system endocannibinoid release (32), all of which are potential candidates for abrogating hypothalamic endocrine and downstream reproductive axis functions.
    • Nathan Goodyear
       
      The HPA axis effect may be the result of inflammation.
  • The relationship between obesity and T can be bidirectional: low T may be the cause rather than consequence of obesity
  • chronic alcohol abuse is known to suppress LH (40), our data showed no significant association among the three hormones or SHBG and alcohol intake.
  • increase in total T in smokers occurs through a primary increase in SHBG with a compensatory rise in LH
  • the effects of obesity (BMI or waist circumference) was by far the most important determinant of variance in total T, whereas age per se was important for SHBG, LH, and free T with comorbidity and smoking being comparatively minor contributors
  • It is noteworthy that these predisposing lifestyle and health factors are modifiable. This implies that the apparent age-related decline in T may constitute a barometer of health and thus be potentially preventable and/or reversible.
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    Age induced decline in Testosterone is more associated with a decline in leydig cell function and thus elevated LH will be associated.  In contrast, obesity is more of a HPA axis disruption and thus LH may be normal to low.  The pulse amplitude is decrease.  No change in pulse frequency is noted.   With obesity, a decline in TT and fT was independent of SHBG. Aging is associated with a greater decrease in fT versus TT.
Nathan Goodyear

Utility of Salivary Cortisol Measurements in Cushing's Syndrome and Adrenal Insufficiency - 1 views

  • It is expected that the use of the measurement of salivary cortisol will become routine in the evaluation of patients with disorders of the HPA axis.
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    Salivary cortisol testing shown to have sensitivity and specificity that exceeds 90%.  Final Quote: "salivary cortisol will become routine in the evaluation of patients with disorders of the HPA axis
Nathan Goodyear

Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. - P... - 0 views

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    Leptin inhibits CRH, thus decreasing the HPA axis.
Nathan Goodyear

Acute Glucocorticoid Deficiency and Diabetes Insipidus Are Common After Acute Traumatic... - 0 views

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    High rate (78%) of those post TBI have low cortisol levels due to damaged HPA axis.  Low cortisol levels post TBI are associated with an increase mortality rate and increased long-term HPA disruption.
Nathan Goodyear

Sex differences in the adult HPA axis and affectiv... [Brain Res. 2014] - PubMed - NCBI - 0 views

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    Animal study finds that Bisphenol A exposure in utero has profound different effects in male offspring versus female offspring.  In the male offspring there appears to be an up regulation of the HPA axis.  The opposite appears true in the female off spring.  Additionally, the receptors are effected differently as well.
Nathan Goodyear

The hypothalamic-pituitary-adrenal axis and sex hormones in chronic stress and obesity:... - 0 views

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    Very nice article on the thoughts currently involving stress, overactivity of the HPA axis and obesity.
Nathan Goodyear

Social Support and Salivary Cortisol in Women With Metastatic Breast Cancer - 0 views

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    better cortisol pattern seen in women with good social support.  This is indicative of a better balanced HPA axis and thus immune system balance.  Significant implications in women with metastatic breast cancer.  Cortisol evaluated by saliva
Nathan Goodyear

Salivary cortisol as a biomarker in stress researc... [Psychoneuroendocrinology. 2009] ... - 0 views

  • psychobiological mechanisms, which trigger the hypothalamus-pituitary-adrenal axis (HPAA) can only indirectly be assessed by salivary cortisol measures. The different instances that control HPAA reactivity (hippocampus, hypothalamus, pituitary, adrenals) and their respective modulators, receptors, or binding proteins, may all affect salivary cortisol measures.
  • linear relationship with measures of plasma ACTH and cortisol in blood or urine does not necessarily exist
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    saliva cortisol testing is a better assessment tool for HPA axis function, compared to serum cortisol
Nathan Goodyear

The effect of common genetic variati... [J Clin Endocrinol Metab. 2012] - PubMed - NCBI - 0 views

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    hyperactive HPA axis associated with depression. This is becoming evident in the literature.  This study looked at SNPS in the etiology of elevated cortisol and/or androstenedione.  They followed the results with saliva and found that 3 SNPS were associated with increased 11Beta-HSD1 activity and associated increased depression.
Nathan Goodyear

Decreased cortisol awakening respon... [Psychoneuroendocrinology. 2005] - PubMed - NCBI - 0 views

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    early life stressors shown to reduce morning cortisol on salivary testing.  This indicates an altered HPA axis.
Nathan Goodyear

Diagnosis of secondary adrenal insufficiency in patients with hypothalamic-pituitary di... - 0 views

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    European journal of endocrinology article compared serum to salivary cortisol and found them to be equal, but due to ease of collection, salivary cortisol to be preferable.  This article was using cortisol to assess HPA axis dysfunction.
Nathan Goodyear

Circadian disruption in cancer: a neuroend... [Brain Behav Immun. 2003] - PubMed - NCBI - 0 views

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    disrupted cortisol rhythm or pattern due to stress is a pathway to disease.  A disrupted HPA axis is a disrupted immune system.
Nathan Goodyear

Anxiety disorders and salivary cort... [Psychoneuroendocrinology. 2012] - PubMed - NCBI - 0 views

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    low am cortisol, found in adults with "long-lasting" anxiety.  The proposed reason is a physiologic down regulation of the HPA axis.
Nathan Goodyear

The morning salivary cortisol response in burnout. [J Psychosom Res. 2005] - PubMed result - 0 views

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    cortisol salivary testing.  elevated am cortisol reflective of HPA axis dysfunction due to stress.
Nathan Goodyear

Sex hormone synthesis, regulation, and function | McMaster Pathophysiology Review - 0 views

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    Good review of the HPA-sex hormone pathways, called the Hypothalamic-Pituitary-Gondal axis, including HP feedback.  This is not a study but has nice diagrams. This is based on 14 referenced articles and 1 book chapter.
Nathan Goodyear

Hypothalamic-pituitary-adrenal stress axis function and the relationship with chronic w... - 0 views

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    Those with chronic pain shown to have HPA dysfunction.  Elevated cortisol was found via saliva evaluation.  This with pain had the higher cortisol levels.
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