Search PubMed⌕ Search

Biomedical subjects

R H Straub

Publications and source records attributed to R H Straub.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cytokines and hormones as possible links between endocrinosenescence and immunosenescence.

Deterioration of the immune system and the endocrine system during aging is thought to contribute to increased morbidity and mortality. Since bidirectional interrelations of both systems are present in the young and in the elderly, endocrinosenescence modulates the immune system and immunosenescence changes the endocrine system. This review focuses on age-related changes of the two systems and provides examples for the interaction of both systems during aging. It is demonstrated that both systems modulate each other in a probably unfavorable way which may be a cofactor in the aging process. Understanding of these bidirectional physiological mechanisms will help to define targets for therapeutical intervention to improve the health of aging people.

Aging↗
PubMed2000

Neurotransmitters of the sympathetic nerve terminal are powerful chemoattractants for monocytes.

Macrophages in lymphoid organs are in close contact to nerve terminals of the sympathetic nervous system. Hence, these cells could be targets of neuronal modulation. We studied sympathetic neurotransmitters as chemoattractants enabling the aggregation of macrophages and nerve terminals. Norepinephrine (NE), neuropeptide Y (NPY), isoproterenol (beta-adrenergic), p-aminoclonidine (alpha2-adrenergic), methoxamine (alpha1-adrenergic), and adenosine triphosphate (ATP) were used to study human monocyte and macrophage migration in 48-well Boyden chambers. NE stimulated chemotaxis of monocytes and macrophages at an optimal concentration of 10-(10) M (P < 0.025). Isoproterenol, but not p-aminoclonidine or methoxamine, induced chemotaxis of monocytes (10(-10) M, P < 0.05). In these studies, elevation of cAMP is a critical step in NE-induced chemotaxis of monocytes. NPY (10(-11) M, P < 0.05) stimulated monocyte chemotaxis as well. ATP at 10(-4) and 10(-5) M stimulated undirected cell mobility (P < 0.05). All tested neurotransmitters of the sympathetic nerve terminal were potent chemoattractants. These findings may explain the close association of nerves and macrophages in tissue and lymphoid organs and may thus be of functional relevance in neuroimmunomodulation.

Chemotactic Factors↗
PubMed2000

Modulation of IL-6 production during the menstrual cycle in vivo and in vitro.

During the menstrual cycle (MC), premenopausal women experience changes in basal temperature and their physical condition and well-being. Premenopausal female patients with chronic inflammatory diseases demonstrate changes in disease activity during the MC. The study was initiated to explore reasons for these phenomena. The sex hormone-modulated lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) secretion in a whole blood assay, serum IL-6 concentration, and serum sex hormone concentrations were studied throughout the MC in five healthy female subjects (median, 28 years; mean, 31.2+/-2.2 years, 26-38 years). Serum IL-6 concentration demonstrated a significant increase in the luteal phase of the MC and was elevated when serum dehydroepiandrosterone (DHEA) was low and vice versa. DHEA decreased LPS-induced IL-6 secretion at six of seven time points during the MC (DHEA, p = .047). In contrast, beta-estradiol and testosterone increased LPS-induced IL-6 secretion in six of seven time points during the MC (significant for testosterone, p = .005). The study demonstrates oscillation of serum IL-6 concentration during the MC and the marked MC-dependent modulation of IL-6 secretion by sex hormones. These mechanisms may be involved in the changes in the basal temperature, the general condition, and, in patients with chronic inflammatory diseases, of disease activity during the MC.

Adult↗
PubMed2000

Autonomic neuropathy in patients with HIV: course, impact of disease stage, and medication.

The purpose of this article is to examine the prevalence, degree, and natural course of pupillary neuropathy (PANP), cardiovascular autonomic neuropathy (CANP), and sensorimotor neuropathy (SNP) and to study the impact of disease stage and medication on neuropathy in 61 consecutive patients with HIV. PANP, CANP, and SNP were assessed by standardized test procedures. Overall prevalence of PANP, CANP, and SNP were 66%, 15%, and 15%, respectively. The maximal pupillary area (pupillary measure, p <0.0001) and the lying-to-standing ratio (cardiovascular measure, p <0.0001) were abnormal as compared with control subjects. The changes in CD4+ T-lymphocytes and respiratory sinus arrhythmia percentile during 2 years of follow-up correlated significantly (r = 0.758, p = 0.007). Patients with CANP were more often in an advanced disease stage than patients without CANP (p = 0.004). SNP, but not PANP or CANP, was associated with the intake of the neuropathogenic drugs dideoxycytidine, dideoxyinosine, and 2',3' didehydro-2',3' dideoxythymidine (p <0.05). Autonomic and sensorimotor neuropathy are frequent in patients with HIV, and progression of CANP may put patients at risk for unexpected cardiorespiratory arrest.

Adult↗
PubMed2000

Stress and rheumatic diseases.

This study was done to review the literature concerning the influence of minor and major stress factors on onset and course of rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), systemic lupus erythematosus (SLE), and fibromyalgia syndrome (FS). Major life events and chronic minor stress seem to be very important factors in JCA and are significantly associated with the onset of the disease. With respect to RA and FS, stress may be a provoking factor but the data in the literature are equivocal. However, during the course of the disease, minor stress aggravates SLE, FS, JCA, and RA. Patients with FS and RA may profit from psychological therapies. Optimistic and confronting coping strategies were found most frequently and perceived to be most effective. Very important for psychological function is the social background, especially the functioning of the family is of outstanding importance for clinical and psychological outcome.

Adaptation, Psychological↗
PubMed2000

Neuropeptide Y cotransmission with norepinephrine in the sympathetic nerve-macrophage interplay.

The CNS modulates immune cells by direct synaptic-like contacts in the brain and at peripheral sites, such as lymphoid organs. To study the nerve-macrophage communication, a superfusion method was used to investigate cotransmission of neuropeptide Y (NPY) with norepinephrine (NE), with interleukin (IL)-6 secretion used as the macrophage read-out parameter. Spleen tissue slices spontaneously released NE, NPY, and IL-6 leading to a superfusate concentration at 3-4 h of 1 nM:, 10 pM:, and 120 pg/ml, respectively. Under these conditions, NPY dose-dependently inhibited IL-6 secretion with a maximum effect at 10(-10) M: (p = 0.012) and 10(-9) M: (p < 0.001). Simultaneous addition of NPY at 10(-9) M: and the alpha-2-adrenergic agonist p-aminoclonidine further inhibited IL-6 secretion (p < 0.05). However, simultaneous administration of NPY at 10(-9) M: and the beta-adrenergic agonist isoproterenol at 10(-6) M: or NE at 10(-6) M: significantly increased IL-6 secretion (p < 0.005). To objectify these differential effects of NPY, electrical field stimulation of spleen slices was applied to release endogenous NPY and NE. Electrical field stimulation markedly reduced IL-6 secretion, which was attenuated by the NPY Y1 receptor antagonist BIBP 3226 (10(-7) M, p = 0.039; 10(-8) M, p = 0.035). This indicates that NPY increases the inhibitory effect of endogenous NE, which is mediated at low NE concentrations via alpha-adrenoceptors. Blockade of alpha-adrenoceptors attenuated electrically induced inhibition of IL-6 secretion (p < 0.001), which was dose-dependently abrogated by BIBP 3226. This indicates that under blockade of alpha-adrenoceptors endogenous NPY supports the stimulating effect of endogenous NE via beta-adrenoceptors. These experiments demonstrate the ambiguity of NPY, which functions as a cotransmitter of NE in the nerve-macrophage interplay.

Adrenergic Agonists↗
PubMed2000

The adrenal steroid status in relation to inflammatory cytokines (interleukin-6 and tumour necrosis factor) in polymyalgia rheumatica.

OBJECTIVES: To determine the correlation between inflammatory cytokines and adrenal hormones in patients with polymyalgia rheumatica (PMR) and to compare the ratio of serum cortisol and androstenedione (ASD) or dehydroepiandrosterone sulphate (DHEAS) in normal subjects with PMR patients. METHODS: In 102 patients with PMR (32 beginning and 70 chronic disease) and 31 age-matched and sex-matched healthy subjects, ASD, cortisol, DHEAS, interleukin-6 (IL-6), and tumour necrosis factor (TNF) were measured by immunometric assays. RESULTS: Serum levels of IL-6 were elevated in patients with PMR as compared with normal subjects (10.0 +/- 1.6 vs 2.1 +/- 0.1 pg/ml, P = 0.01), which was not found for TNF. In PMR patients, serum levels of IL-6 were positively correlated with serum levels of ASD (P < 0.001), cortisol (P < 0.001), and DHEAS (P = 0. 038) irrespective of corticosteroid treatment. Serum levels of cortisol in relation to IL-6 were significantly lower in patients with chronic disease and long-standing corticosteroid administration as compared with patients with recent onset of the disease and without corticosteroid therapy (P < 0.01). CONCLUSIONS: In PMR, as expected, there was an increase in IL-6 serum levels that was associated with elevated serum levels of ASD, DHEAS, and cortisol which was more marked in patients with recent-onset disease and without corticosteroids. However, serum levels of cortisol in patients with and without corticosteroids were lower than expected by considering the inflammatory status (increased IL-6). This may indicate a change in the hypothalamic-pituitary-adrenal (HPA) axis responsiveness to inflammatory stimuli such as IL-6 during chronic disease. Furthermore, there seems to be a shift of biosynthesis to cortisol in relation to DHEAS or ASD in chronic disease.

Adrenal Glands↗
PubMed2000

A bacteria-induced switch of sympathetic effector mechanisms augments local inhibition of TNF-alpha and IL-6 secretion in the spleen.

It is believed that an inflammation-induced activation of the CNS leads to an inhibition of overshooting immune responses to prevent extensive local cytokine secretion. However, immunosuppression by the sympathetic nervous system may be unfavorable when bacteria are present locally and when TNF-alpha is necessary to overcome infection. We now report in a superfusion model, using mouse spleen slices, that although local Pseudomonas aeruginosa increased splenic TNF-alpha and IL-6 secretion severalfold over basal levels, electrically released neurotransmitters attenuated cytokine secretion to similar basal level as under bacteria-free conditions. Bacteria reversed noradrenergic inhibitory effector mechanisms: Under bacteria-free conditions, TNF-alpha secretion was very low and IL-6 secretion was mainly inhibited by alpha2-adrenoreceptor ligation. In the presence of bacteria, TNF-alpha and IL-6 secretion were high and IL-6 secretion was mainly inhibited by beta-adrenoreceptor ligation. The alpha- to beta-adrenoswitch of IL-6 inhibition in the presence of bacteria was mediated by the prior adrenergic regulation of TNF-alpha. In vivo, chemical abrogation of sympathetic inhibition reduced accumulation of bacteria in the spleen, which depended at least in part on TNF-alpha. This suggests that activation of the sympathetic nervous system may be a forerunner for accumulation of bacteria in tissue and consecutively sepsis due to intensified inhibition of TNF-alpha secretion.

Animals↗
PubMed2000

The loss of sympathetic nerve fibers in the synovial tissue of patients with rheumatoid arthritis is accompanied by increased norepinephrine release from synovial macrophages.

Our objective was to investigate sympathetic and sensory nerve fibers in synovial tissue in rheumatoid arthritis (RA) and osteoarthritis (OA) in relation to histological inflammation and synovial cytokine and norepinephrine (NE) secretion. Immunohistochemistry was used to detect nerve fibers and inflammatory parameters. A superfusion technique of synovial tissue pieces was used to investigate cytokine and NE secretion. In RA, we detected 0.2 +/- 0.04 tyrosine hydroxylase-positive (TH-positive=sympathetic) nerve fibers/mm2 as compared to 4.4 +/- 0. 8 nerve fibers/mm2 in OA (P<0.001). In RA, there was a negative correlation between the number of TH-positive nerve fibers and inflammation index (RRank=-0.705, P=0.002) and synovial IL-6 secretion (RRank=-0.630, P=0.009), which was not found in OA. Substance P-positive (=sensory) nerve fibers were increased in RA as compared to OA (3.5+/-0.2 vs. 2.3+/-0.3/mm2, P=0.009). Despite lower numbers of sympathetic nerve fibers in RA than in OA, NE release was similar at baseline (RA vs. OA: 152+/-36 vs. 106+/-21 pg/ml, n.s.). Basal synovial NE secretions correlate with the number of TH-positive CD 163+ synovial macrophages (RA: RRank=0.622, P=0.031; OA: RRank=0.299, n.s.), and synovial macrophages have been shown to produce NE in vitro. Whereas sympathetic innervation is reduced, sensory innervation is increased in the synovium from patients with longstanding RA when compared to the synovium from OA patients. The differential patterns of innervation are dependent on the severity of the inflammation. However, NE secretion from the synovial tissue is maintained by synovial macrophages. This demonstrates a loss of the influence of the sympathetic nervous system on the inflammation, accompanied by an up-regulation of the sensory inputs into the joint, which may contribute to the maintenance of the disease.

Aged↗
PubMed2000

Hormone replacement therapy and interrelation between serum interleukin-6 and body mass index in postmenopausal women: a population-based study.

Postmenopausal women are at increased risk to develop osteoporosis, coronary artery disease, heart failure, and hypertension. Interleukin-6 (IL-6) may be a pathogenetic element in these disorders. Serum IL-6 levels increase during aging and seem to be related to increased body fat mass. In the present retrospective study we aimed to investigate the role of hormone replacement therapy (HRT) on serum IL-6 levels and the interrelation of IL-6 and body fat mass. Parameters were assessed in a population-based sample of postmenopausal women (n = 302) and, for comparison, 245 men of the same age. Women with HRT (n = 92) had significantly lower serum IL-6 levels compared to subjects without HRT, which was independent of age, antihypertensive therapy, smoking habits, and blood pressure (1.5 +/- 0.1 vs. 2.9 +/- 0.6 pg/mL; P = 0.017). In women without HRT, the body mass index (BMI) was correlated with serum IL-6 levels (P < 0.001). Multivariate analysis controlling simultaneously for the effects of blood pressure and heart rate confirmed the positive correlation (P = 0.001). However, in subjects with HRT no such correlation between IL-6 and BMI was demonstrated, which was confirmed after controlling covariates. In male subjects, BMI correlated with serum IL-6 (P = 0.009), which was, however, blunted after controlling for blood pressure and heart rate, probably indicating an influence of the sympathetic nervous system on this interrelation. In conclusion, women receiving HRT display lower serum IL-6 levels and a blunted interrelation of IL-6 and BMI. As IL-6 may be a pathogenetic factor in age-related diseases, HRT-related inhibition of IL-6 secretion could be an important element for the favorable effects of HRT in postmenopausal women.

Aged↗
PubMed2000

Conversion of dehydroepiandrosterone to downstream steroid hormones in macrophages.

Dehydroepiandrosterone (DHEA) is a ubiquitous adrenal hormone with immunomodulatory effects such as inhibition of the production of monokines. Whether DHEA itself or the downstream steroids are the immunomodulatory effector hormones in target cells is not known. In this study, we investigated the conversion of DHEA to downstream steroid hormones in target macrophages. Within 1 day of culture with radiolabeled DHEA, monocyte-derived macrophages converted DHEA to significant amounts of Delta5-derivatives such as 16OH-DHEA, 3beta, 17beta-androstenediol (A'diol), and 3beta,16alpha, 17beta-androstenetriol (A'triol). However, the production of Delta4-steroids (androstenedione (A'dione), testosterone (T), and 16OH-T) and estrogens (estrone, estradiol, and estriol) was relatively low. Further cultivation of macrophages for 5 days with radiolabeled DHEA resulted in a significant (P<0.05) increase of the molar amounts of A'triol (P=0.012), 16OH-T (P=0.008), and estriol (P=0.003). In contrast to monocyte-derived macrophages, monocytes did not express aromatase mRNA, which was demonstrated by RT-PCR (P<0.01). Furthermore, DHEA in macrophages significantly inhibited one of the downstream converting enzymes, the aromatase, which was not demonstrated in the presence of the typical macrophage activator, lipopolysaccharide (LPS) (P<0.01). In conclusion, conversion of DHEA to physiologically relevant amounts of Delta5- and Delta4-steroids and estrogens was demonstrated in monocyte-derived macrophages. The conversion depends on maturation of monocytes and local factors such as the presence of LPS. The conversion of DHEA leads to an increase of downstream effector hormones in target macrophages which may be an important factor for local immunomodulation.

Aromatase↗
PubMed2000

Altered function of the hypothalamic stress axes in patients with moderately active systemic lupus erythematosus. I. The hypothalamus-autonomic nervous system axis.

OBJECTIVE: To determine the human corticotropin releasing hormone (hCRH) induced stress response of the hypothalamus-autonomic nervous system axis (HANS) in patients with moderately active systemic lupus erythematosus (SLE). METHODS: Cardiovascular and pupillary function variables were measured by standardized computer procedures before and during an hCRH test (6 time points). The results of 12 patients with SLE were compared to 24 healthy subjects with (HS+P, n = 12) and without (HS, n = 12) prior administration of prednisolone 3 days before the test. RESULTS: At baseline, diastolic blood pressure was significantly higher in SLE than in HS or HS+P (p<0.001). During the hCRH test, patients with SLE had increased heart rates and systolic and diastolic blood pressure responses compared to HS+P and HS (p<0.001 for all comparisons). Moreover, heart rate variation was decreased at rest, during the lying-to-standing procedure, and during the 2 applied respiratory tests (p<0.01 vs. HS). Compared to HS+P and HS, latency time of the pupillary light reflex was prolonged and maximal pupillary area was increased, revealing sympathetic hyperreactivity. CONCLUSION: This study found an altered autonomic nervous system response at baseline, which was more pronounced during the hCRH stress test in patients with moderately active SLE compared to healthy subjects. Baseline and stress responses are characterized by a sympathetic overstimulation. Such a hypersympathetic reaction may lead to increased risk of cardiovascular diseases in patients with moderately active SLE, which needs to be investigated in longitudinal studies.

Adrenocorticotropic Hormone↗
PubMed2000

Altered function of the hypothalamic stress axes in patients with moderately active systemic lupus erythematosus. II. Dissociation between androstenedione, cortisol, or dehydroepiandrosterone and interleukin 6 or tumor necrosis factor.

OBJECTIVE: To investigate adrenocorticotropin, androstenedione (ASD), cortisol, or dehydroepiandrosterone sulfate (DHEAS) before and during a corticotropin releasing hormone (hCRH) test in patients with moderately active systemic lupus erythematosus (SLE) undergoing low dose longterm glucocorticoid therapy, and to examine these hormones in relation to interleukin 6 (IL-6) or tumor necrosis factor (TNF). METHODS: Serum levels of hormones and cytokines were measured before and during an hCRH test. The results of 12 patients with SLE were compared to 12 healthy subjects (HS) and 12 healthy subjects given prior short term prednisolone (HS+P). RESULTS: Baseline and stimulated serum ASD, cortisol, and DHEAS were lower in patients with SLE vs. HS (p<0.005), but baseline and stimulated plasma adrenocorticotropin was normal in SLE. In SLE, but not in HS+P or HS, baseline and stimulated DHEAS was low in relation to cortisol or ASD (i.e., shift from DHEAS to cortisol or ASD). In patients with SLE, baseline and stimulated serum levels of adrenal hormones were lower in relation to IL-6 or TNF compared to HS or HS+P (p< 0.001). In contrast, in SLE patients, the baseline and stimulated pituitary hormone adrenocorticotropin was normal in relation to these cytokines. CONCLUSION: We found marked adrenal insufficiency and a shift in steroidogenesis to cortisol in patients with SLE, but a completely normal pituitary function (in absolute values and in relation to IL-6 or TNF). This may depend in part on prior longterm glucocorticoid therapy and changes of steroidogenesis due to cytokines. The situation in patients with SLE was not mimicked by high dose short term prednisolone in healthy subjects. Further longitudinal studies in untreated patients are needed to investigate the endocrine-immune interplay and its consequences during the course of SLE.

Adrenocorticotropic Hormone↗
PubMed2000

Neurotransmitter modulation of interleukin 6 (IL-6) and IL-8 secretion of synovial fibroblasts in patients with rheumatoid arthritis compared to osteoarthritis.

OBJECTIVE: The sensory nervous system with the 2 neurotransmitters substance P (SP) and calcitonin gene related peptide (CGRP) is proinflammatory in experimental models of arthritis. The role of the sympathetic nervous system with norepinephrine (NE), adenosine, beta-endorphin, and methionine enkephalin (MENK) is not clearly understood. We studied the influence of these neurotransmitters on secretion of interleukin 6 (IL-6) and IL-8 in primary cultures of synovial fibroblasts of patients with rheumatoid arthritis (RA) compared to osteoarthritis (OA). METHODS: Fibroblasts were isolated using fresh synovial tissue of 5 patients with RA and 5 with OA who underwent knee joint replacement surgery. Modulation of spontaneous secretion of IL-6 and IL-8 was investigated in vitro using the neurotransmitters noted above. RESULTS: In RA fibroblasts, CGRP increased IL-6 and IL-8 secretion at 10(-10) to 10(-8) M (p at least < 0.01), which was not observed in OA fibroblasts. SP had no effect on either cytokine in RA fibroblasts but stimulated IL-8 secretion at 10(-8) M in OA fibroblasts (p < 0.01). In RA fibroblasts, adenosine and NE inhibited secretion of both cytokines at low concentrations (10(-8) M; p < 0.01). However, in OA fibroblasts there was a NE induced increase of IL-8 and IL-6 secretion at 10(-7) and 10(-6) M (p < 0.01), but no inhibition at lower concentrations (10(-8) M; p = NS). In RA fibroblasts, beta-endorphin and MENK inhibited IL-8 secretion at 10(-9) to 10(-7) M (p < 0.01), whereas in OA fibroblasts the dose response curve was shifted to lower concentrations (10(-12) M, 10(-11) M; p < 0.01). CONCLUSION: In OA fibroblasts, the sympathetic neurotransmitters were stimulatory at higher concentrations. CGRP was the most potent stimulatory neurotransmitter in RA fibroblasts whereas the sympathetic adenosine, NE, beta-endorphin, and MENK were inhibitory. This indicates a dualism of action of sympathetic and sensory neurotransmitters, with inhibitory and stimulatory effects on cytokine secretion of RA fibroblasts.

Aged↗
PubMed2000

Replacement therapy with DHEA plus corticosteroids in patients with chronic inflammatory diseases--substitutes of adrenal and sex hormones.

A dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis was found in animal models of chronic inflammatory diseases, and the defect was located in more central portions of the HPA axis. This defect of neuroendocrine regulatory mechanisms contributes to the onset of the model disease. Since these first observations in animal models were made, evidence has accumulated that the possible defect in the HPA axis in humans is more distal to the hypothalamus or pituitary gland: In chronic inflammatory diseases, such as rheumatoid arthritis, an alteration of the HPA stress response results in inappropriately low cortisol secretion in relation to adrenocorticotropic hormone (ACTH) secretion. Furthermore, it has recently been shown that the serum levels of another adrenal hormone, dehydroepiandrosterone (DHEA), were significantly lower after ACTH stimulation in patients with rheumatoid arthritis without prior corticosteroids than in healthy controls. These studies clearly indicate that chronic inflammation alters, particularly, the adrenal response. However, at this point, the reason for the specific alteration of adrenal function in relation to pituitary function remains to be determined. Since one of the down-regulated adrenal hormones, DHEA, is an inhibitor of cytokines due to an inhibition of nuclear factor-kappa B (NF-kappa B) activation, low levels of this hormone may be deleterious in chronic inflammatory diseases. We have recently demonstrated that DHEA is a potent inhibitor of IL-6, which confirmed an earlier study in mice. Since IL-6 is an important factor for B lymphocyte differentiation, the missing down-regulation of this cytokine, and others such as TNF, may be a significant risk factor in rheumatic diseases. Since in these patients, administration of prednisolone or the chronic inflammatory process itself alters adrenal function, endogenous adrenal hormones in relation to proinflammatory cytokines change. Furthermore, these mechanisms may also lead to shifts in steroidogenesis which have been demonstrated in chronic inflammatory diseases. It was repeatedly demonstrated that the serum level of the sulphated form of DHEA (DHEAS) was significantly lower in patients with chronic inflammatory diseases. Since DHEAS is the pool for peripheral sex steroids, such as testosterone and 17 beta-estradiol, lack of this hormone leads to a significant sex hormone deficiency in the periphery. This overview will demonstrate mechanisms why DHEAS is reduced in chronic inflammatory diseases. The importance of DHEAS deficiency will be demonstrated with respect to osteoporosis. As a consequence, we suggest a combined therapy with corticosteroids plus DHEA in chronic inflammatory diseases.

Adrenal Cortex Hormones↗