Biology Reference
In-Depth Information
pituitary, IL-11 and CNTF had no significant effect on the release of either GH or
PRL, or on GH mRNA. However, when the cells were cultured in aggregates, in
which the three-dimensional structure of the cells is reconstituted, both CTKs, in
doses at which they had no effect on monolayer cultures, significantly stimulated
both PRL and GH secretion
[46]
.
The presence of L-NAME (1 mM), an inhibitor of NO synthase (NOS), in the
incubation medium significantly blunted the inhibition of PRL release produced by
TNF- (50 ng/ml) in female rats. TNF- increased nitrite release to the incubation
medium. The activity of NOS was significantly enhanced when anterior pituitary
cells were incubated with TNF- for 8 hours or more. Also, TNF- induced iNOS
gene expression in anterior pituitary cells
[47]
.
Stromal cell-derived factor-1 (SDF1), via its receptor CXCR4, stimulated the pro-
liferation of the pituitary adenoma cell line GH4C1, and released both PRL and GH
through a complex network of intracellular signals
[48]
.
C3a receptors are expressed in pituitary hormone-secreting and nonhormone-se-
creting (folliculostellate) cells. Both C3a and C3adesArg (a noninflammatory metab-
olite) stimulate pituitary cell cultures to release PRL, GH, and adrenocorticotropin.
Serum levels of these hormones, together with adrenal corticosterone, increase dose
dependently with recombinant C3a and C3adesArg administration
in vivo
[49]
.
Erythropoetin administration to patients with amyotrophic lateral sclerosis
caused a significant reduction of serum PRL levels, maximal 60 minutes after admin-
istration
[50]
.
GCs and CATs stimulate IL-4, IL-10, and transforming growth factor (TGF),
which exert negative feedback on excess CTK production during APR
[51]
. These
CTKs are produced by Tsrs
[28]
.
Several mechanisms have been proposed for conveying the CTK signal across
the blood-brain barrier (BBB). Once the signal is transmitted across the BBB, the
signal travels through neural pathways as follows: area postrema→nucleus tractus
solitarius→ventrolateral medulla→paraventricular nucleus, which initiates HPA axis
responses. Descending pathway: PVN→brainstem cell groups→thoracic spinal cord
preganglionic neurons→via sympathetic projections to the end organs such as the
thymus and spleen
[52]
.
Several of the effects of pro-inflammatory CTKs exerted in a “healthy” brain are
amplified in the CNS by the following mechanisms: (a) peripheral CTKs, such as
IL-1, have the capacity to elicit their own synthesis in the brain; and (b) a sustained
increase in neuronal activity also induces production of physiologically significant
amounts of these mediators. The brain-borne IL-1 and IL-6 fulfill physiological roles
when their production is not the result of pathological events in the CNS. These
CTKs stimulate the HPA axis, and they are involved in physiologic brain mechanisms
such as synaptic plasticity, memory formation, and the control of glucose homeosta-
sis
[53]
. CTKs are now being investigated also for their synaptic and inflammatory
action in the CNS. These proteins and their receptors can be synthesized in the brain
by glial and neuronal cells and contribute to two main types of action: modulation of
neuronal excitability and local inflammatory responses
[54]
.
