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Alfa
1 Adrenergic Potentiation of Progesterone Accumulation Stimulated
by
Vasoactive Intestinal Peptide (VIP) and Pituitary Adenylate
Cyclase -
Activating Polypeptide (PACAP) in Cultured Rat Granulosa Cells
Elzbieta Wasilewska-Dziubiñska,
Monika Borowiec,
Magdalena Chmielowska,
Ewa Woliñska-Witort
Boguslawa Baranowska
Department
of Clinical Neuroendocrinology, Medical Centre of Postgraduate
Education, Fieldorfa 40, 04-158 Warsaw, POLAND.
Submitted:
October 29, 2001
Accepted: November 18, 2001
Key words:
VIP, PACAP, progesterone, phenylonephrine, fenoterol, 25-hyroxycholesterol,
culture of rat granulosa cells
Abstract
OBJECTIVE:
VIP and PACAP, two structurally related peptides, stimulate
c AMP, steroidogenesis and progesterone (PROG) release from
cultured rat granulosa cells. VIP and PACAP38 are known to
mimic the effects of b-adrenergic
receptor stimulation in the rat pinealocytes causing an increased
melatonin synthesis. These effects were markedly potentiated
by a1 adrenergic receptor stimulation.
METHODS:
We examined the influence of phenylonephrine (PHEN) (10-4
M and 10-5 M)-a1 adrenergic receptor
agonist and fenoterol (FEN) (10-5 M)-b2
adrenergic receptor agonist on PROG accumulation stimulated
by VIP (10-6 M) and PACAP (10-7 M) in cultured ovarian granulosa
cells of cyclic rats (diestrus) after 2 h and 24 h incubation.
The PROG concentrations in supernatants were measured with
RIA tests.
RESULTS:
VIP, PACAP38, PHEN and FEN stimulated PROG accumulation after
2 h incubation. The PROG accumulation stimulated both by FEN
and VIP, and by FEN and PACAP38 was not additive. PROG accumulation
stimulated by VIP and PACAP38 was strongly potentiated by
PHEN-a1 adrenergic agonist.
CONCLUSION:
The a1 adrenergic potentiation
of VIP and PACAP38 stimulatory effects on PROG release from
granulosa cells culture was found. VIP, PACAP38 and
b2 adrenergic receptors activation may share the same
postreceptor mechanism. There exists simultaneous activation
of different receptors - peptidergic and adrenergic ones in
cultured granulosa cells of adult cyclic rat.
Introduction
It
has been reported that in the rat, development of the ovarian
innervation preceedes the onset of folliculogenesis and occurs
before follicles acquire responsivenness to gonadotropins, [1].
VIP [2,3] and norepinephrine (NE) [4], the neurotransmitters
contained in ovarian nerves are present in the ovary before
the gland becomes responsive to gonadotropins and are able to
act on early follicles to facilitate the process of molecular
differentiation that leads to gonadotropin dependency [5]. In
the rat ovary both VIP and NE act via specific receptors coupled
to cAMP-generating system, VIP through VIP receptor type 2 [6]
VPAC 2 known as PVR 3 or PACAP typ 3 receptor [7] and NE via
b2- adrenergic receptors [8, 9].
Pituitary
gonadotropins (FSH, LH) are the most important hormones regulating
different ovarian functions. However, the studies on cultured
granulosa cells demonstrated the important intra- ovarian regulatory
role of several steroidal and nonsteroidal factors [10] including
neuropeptides and catecholamines. Previous studies demonstrated
that VIP [11] and PACAP [12, 13], members of glucagon/secretin
structurally related peptides family, stimulate cAMP, steroidogenesis
and progesterone (PROG) accumulation in cultured rat granulosa
cells in the presence or absence of FSH. These effects of maximally
effective concentrations of VIP and PACAP on progesterone secretion
were not additive [13]. The local ovarian synthesis of VIP is
also suggested by ability to detect VIP mRNA within rat ovarian
tissue [14]. VIP can regulate cytochrome P 450 cholesterol side-chain
cleavage (P 450 scc) enzyme gene expression (partially mediated
through cAMP) in granulosa cells from estrogen-primed immature
rats [15] and the synthesis of P 450 scc enzyme complex [16]
responsible for the first reaction in PROG biosynthesis [17,18].
The results suggest that the stimulatory effect of VIP on ovarian
PROG secretion involves regulation of ... ...
Moreover,
PACAP secreted from these cells may induce dose-dependent PROG
accumulation suggesting that PACAP could be an auto- or paracrine
regulator of ... ...
...
...
The
Aim
Materials
and Methods
Results
Results Short-term experiments ... ...
Long-term experiments ... ....
Discussion
... ....
In conclusion: ... ....
Acknowledgments
The paper was supported by the scientific program No. 501-2-2-25-93/01
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