Related Experiment Videos
Characterization of the effect of Mycoplasma fermentans on the hypothalamo-pituitary-adrenal axis
A Wohlman1, R Gallily, R Yirmiya
1Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
Abstract:
The mechanisms involved in the activation of the hypothalamus-pituitary-adrenal axis after administration of Mycoplasma fermentans were examined. Male rats were injected intracerebroventricularly (i.c.v.) with heat-inactivated M. fermentas (6 micrograms protein/10 microliters/rat) or vehicle and were killed 2 h later. M. fermentans caused a significant depletion of corticotropin releasing hormone (CRH-41) content in the median eminence (ME), and elevation of serum ACTH and corticosterone (CS) levels, compared to control levels. Pretreatment with dexamethasone (DEX, 40 micrograms/kg) markedly inhibited M. fermentans-induced depletion of ME CRH-41 and the increase in serum ACTH and CS. Injection of the type II corticosteroid receptor antagonist RU-38486, but not the type 1 antagonist RU-28318, enhanced the adrenocortical response and completely abolished the inhibitory effect of DEX following M. fermentans. Injection of the catecholamine neurotoxin 6-hydroxydopamine into the ventral noradrenergic bundle, which significantly depleted hypothalamic norepinephrine content, or i.c.v. injection of the specific alpha 1-adrenergic receptor antagonist prazosin failed to affect the adrenocortical response to M. fermentans. In contrast, these agents markedly inhibited the adrenocortical response following i.c.v. injection of interleukin-1. I.c.v. administration of M. fermentans caused a significant elevation of hypothalamic levels of tumor necrosis factor-alpha (TNF alpha), determined by both bioassay and immunoassay. In rats treated with pentoxifylline, an inhibitor of TNF alpha synthesis, the adrenocortical response to M. fermentans was markedly inhibited. These findings suggest that: (1) M. fermentans-induced activation of the pituitary-adrenal axis, and the inhibitory effect of DEX on this response, are mediated by a reduction of CRH-41 release from the ME. (2) The feedback exerted by glucocorticoids is mediated by type II corticosteroid receptors. (3) In contrast to the adrenocortical response to interleukin-1 beta, the central noradrenergic system does not have an important role in mediating the adrenocortical response to M. fermentans. (4) Hypothalamic TNF alpha production is probably involved in mediating the adrenocortical activation following M. fermentans.
Insights
Mycoplasma fermentans activates the hypothalamus-pituitary-adrenal axis by reducing corticotropin-releasing hormone (CRH-41) release, with tumor necrosis factor-alpha (TNF alpha) involvement. Glucocorticoid feedback is mediated by type II corticosteroid receptors.
Area of Science:
- Neuroendocrinology
- Immunology
- Microbiology
Background:
- The hypothalamus-pituitary-adrenal (HPA) axis regulates the stress response.
- Mycoplasma fermentans is a pathogen that can elicit immune responses.
- Understanding how microbial components activate the HPA axis is crucial for deciphering host-pathogen interactions.
Purpose of the Study:
- To investigate the mechanisms underlying HPA axis activation by Mycoplasma fermentans.
- To determine the role of corticotropin-releasing hormone (CRH-41), corticosteroid receptors, noradrenergic system, and tumor necrosis factor-alpha (TNF alpha) in this response.
Main Methods:
- Rats were injected intracerebroventricularly with heat-inactivated M. fermentans.
- Hormone levels (ACTH, corticosterone) and CRH-41 content were measured.
- Dexamethasone (DEX), corticosteroid receptor antagonists (RU-38486, RU-28318), catecholamine neurotoxin (6-hydroxydopamine), and alpha 1-adrenergic antagonist (prazosin) were used.
- Hypothalamic TNF alpha levels were assessed via bioassay and immunoassay.
- Pentoxifylline was used to inhibit TNF alpha synthesis.
Main Results:
- M. fermentans significantly depleted median eminence CRH-41 and elevated serum ACTH and corticosterone.
- Dexamethasone inhibited these M. fermentans-induced changes.
- Type II corticosteroid receptor antagonist RU-38486 abolished DEX's inhibitory effect.
- Noradrenergic system manipulation did not affect the M. fermentans response but did affect interleukin-1 response.
- M. fermentans increased hypothalamic TNF alpha levels.
- Pentoxifylline inhibited the adrenocortical response to M. fermentans.
Conclusions:
- M. fermentans activates the HPA axis via reduced CRH-41 release from the median eminence.
- Glucocorticoid feedback is mediated by type II corticosteroid receptors.
- The central noradrenergic system is not critical for M. fermentans-induced HPA activation.
- Hypothalamic TNF alpha production is involved in mediating the HPA axis activation by M. fermentans.