Serotonin and the rat adrenal gland.
Serotonin (5HT) is an indoleamine with potent j vitro and in vivo
effects on aldosterone biosynthesis in the adrenal zona glomerulosa
of several species including Man and the rat. Its physiological role
in the control of aldosterone secretion however, is not well
understood. The purpose of these studies was to clarify its
possible role in aldosterone biosynthesis using the rat as an
Attempts to localise 5HT within the adrenal gland using a specific
monoclonal antibody to 5HT with the avidin-biotin detection
technique, suggested, that serotonergic nerves are not present in the
adrenal cortex although appreciable levels of 5HT were measured by
HPLC in adrenal tissue ( 1.7 # 0.2 μg/ g wet weight). The storage
and metabolism of 5HT in isolated zona glomerulosa cells and inner
cortical and, medullary cells was investigated using [3 H]-5HT as a
marker. Zona glomerulosa cells rapidly metabolised 5HT, whereas the
inner zones were able to store or retain 5HT to a greater extent.
Stimulation of steroidogenesis by 5HT however, was confined to the
zona glomerulosa cells of the adrenal cortex.
The interaction of 5HT with specific 5HT receptors was investigated
by studying the effects of the 5HT antagonists, methysergide and
ketanserin on the steroidogenic response to 5HT in isolated zona
glomerulosa cell suspensions. Methysergide (10-6M) inhibited the
corticosterone and aldosterone responses to 5HT (10-9M - 10-6)and
angiotensin II (10-9M, 10-8M). In addition, it significantly inhibited the corticosterone response to ACTH. Ketanserin (10-6M)
also inhibited the corticosterone and aldosterone responses to 5HT
(10-9M, 10-8M) and All (10-9M, 10-8M) but did not affect ACTHstimulated
steroidogenesis. Neither antagonist affected the
steroidogenic responses to potassium.
A change in dietary salt intake of rats did not lead to any
significant change in either the blood levels or adrenal contents of
5HT. The in vitro- responsiveness of adrenal cells to 5HT however,
was altered by changing the sodium status.
An overall view of changing endogenous levels of 5HT in vivo in the
rat was explored using the 5HT-depleting agent, PCPA and the
immediate 5HT-precursor, 5-hydroxytryptophan (5HTP). Treatment with
PCPA led to a decrease in blood 5HT levels and a loss of in vitro
responsiveness to 5HT and All in subsequent preparations of zona
glomerulosa cells. Treatment with 5HTP produced higher blood levels
of 5HT and an enhanced responsiveness of subsequent preparations of
zona glomerulosa cells.
These studies suggest that 5HT from central and/or peripheral sources
such as platelets or mast cells, could exert a tonic effect on
aldosterone secretion from the rat adrenal zona glomerulosa, which is
mediated by the activation of specific receptors for 5HT.