Pan European Networks - Horizon 2020 - page 101

H O R I Z O N 2 0 2 0 P R O J E C T S : P O R TA L
Department of Endocrinology
The Kielanowski Institute of Animal
Physiology and Nutrition
PolishAcademy of Sciences in Jabłonna, Poland
2 0 2 0
reproduction, increased appetite and maternal behaviours. There are also
relevant changes in basal and stress-induced activity of the HPA axis
which have a pivotal role in the metabolic demands of lactating females
and developing offspring. Attenuation of stress-induced activity of the
HPA axis has been observed in almost all studied lactating females,
including rats, sheep and humans.
Suckling appears to be a crucial stimulus that triggers the suppression
of the HPA axis stress response during lactation. In our model, suckling
by lambs significantly suppressed increases in both plasma
adrenocorticotropic hormone (ACTH) and cortisol concentrations in
response to isolation stress in lactating sheep. Using two experimental
in vivo
techniques – intracerebroventricular infusion combined with push-
pull perfusion of the hypothalamic median eminence for simultaneous
administration of salsolinol, or 1-MeDIQ, and identification of the
substances released from the nerve terminals into the hypophyseal portal
system and then to the pituitary gland – we showed numerous changes
in the components of the HPA axis under stress conditions.
Our research points to profound changes with respect to regulating the
stress response that occurs during lactation and the relevant role of
salsolinol at this physiological stage. We suggest that salsolinol mediates
the inhibiting effect of suckling on stress-induced HPA axis activity in
lactating sheep, which would associate this molecule with the mechanism
responsible for reducing the sensitivity of lactating mothers to stressors.
alsolinol is a dopamine derivative that can be found in many areas
of the brain that are rich in dopaminergic neurons. The highest
salsolinol concentrations are detected in the basal ganglia,
especially in the striatum, substantia nigra, frontal cortex and
hypothalamus, as well as in the neurointermediate lobe of the pituitary
gland. Interestingly, it is synthesised during specific physiological and/or
pathophysiological stages in humans and animals.
Numerous studies evaluating the function of salsolinol and in particular,
its methylated derivatives, have revealed their involvement in the
progression of diseases characterised by dysfunctional dopaminergic
neurons. This compound has a molecular structure similar to neurotoxin
6-hydroxydopamine, which is known to induce loss of dopaminergic cells
and elicit symptoms almost identical to idiopathic Parkinson’s disease.
Salsolinol may exert its negative effect by acting at the level of
mitochondria through a reactive oxygen species-activated cascade, or
may induce changes in protein synthesis in the endoplasmic reticulum.
Attention has also been focused on the physiological aspects of
salsolinergic activity within the brain. This compound was shown to be
present at a high concentration within the hypothalamic median
eminence in lactating sheep and in the pituitary gland of lactating rats.
Studies performed at the Kielanowski Institute in Jabłonna revealed that the
extracellular concentration of salsolinol in the sheep median eminence
increased in response to suckling and was closely related to the suckling-
induced increase in the plasma concentration of prolactin.
Intracerebroventricular infusion of exogenous salsolinol in lactating sheep
stimulated prolactin release and increased expression of prolactin mRNA
within the pituitary cells. Moreover, a similar infusion of 1-methyl-3,4-
dihydroisoquinoline (1-MeDIQ), a structural analogue of salsolinol known to
antagonise some of its endogenous actions, inhibited basal prolactin release
and reduced the prolactin surge induced by suckling.
Further studies have shown that salsolinol may mediate in the stimulatory
action of endogenous opioid peptides on the secretion of prolactin in
nursing sheep. The above data indicate the potential character of
salsolinol as a hypothalamic prolactin-releasing factor in lactating
females. It is suggested that it may be an important terminal element in
the suckling stimulus, encouraging the release of prolactin and making
it possible to sustain increased secretion of this hormone during lactation.
Hypothalamic-pituitary-adrenal (HPA) axis
Lactation is characterised by many adaptive changes in morphology,
physiology and maternal behaviour to ensure proper care and
development of the offspring. The postpartum adaptations include, in
addition to the milk production regulated by prolactin, suppressed
Salsolinol – good or evil?
Professor Tomasz Misztal
discusses his investigations on salsolinol, detailing the
impact of salsolinergic activity on a sheep’s hormonal system
© YvonneH
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