During migration and for about 2 days after their arrival in the gonadal ridges, primordial germ cells (the embryonic precursors of gametes of the adult animal) proliferate actively. Certain growth factors, such as stem cell factor and leukemia inhibitory factor, seem to be essential for survival, proliferation and possibly differentiation of mouse primordial germ cell in vivo and/or in vitro. Similarly, increase in intracellular cAMP is followed by a marked enhancement of primordial germ cell proliferation, at least in culture. In the present study, we show that pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP-38), two neuropeptides of the secretin-glucagon-vasoactive intestinal polypeptide-GH-releasing hormone family, stimulate in vitro proliferation of mouse primordial germ cells, bind to primordial germ cells and gonadal somatic cells (possibly to type I PACAP receptor) and activate adenylate cyclase in the same cells. Moreover, PACAP-like immunoreactivity was found in gonadal ridges, mostly on germ cell surface. In conclusion, evidence is provided that PGC proliferation can be stimulated by certain bioactive polypeptides, thus suggesting a novel regulatory role for such compounds in early gonad development.

Reference

Arimura
A.
,
Somogyvari-Vigh
A.
,
Miyata
A.
,
Mizuno
K.
,
Coy
D.
,
Kitada
C.
(
1991
)
Tissue distribution of PACAP as determined by RIA: highly abundant in rat brain and testes.
Endocrinology
129
,
2787
2789
Arimura
A.
(
1992
)
Receptors for pituitary adenylate cyclase-activating polypeptide.
TEM
3
,
288
294
Besmer
P.
(
1991
).
The kit ligand encoded at the murine Steel locus: a pleiotropic growth and differentiation factor.
Curr. Opin. Cell. Biol
3
,
939
946
Chedeville
A.
,
Mirossay
L.
,
Chastre
E.
,
Hurbain-Kosmath
I.
,
Lopez
M.
,
Gespach
C.
(
1993
)
Interaction of VIP and related peptides in normal and leukemic human monocytes and macrophages.
FEBS Lett
319
,
171
176
Cheng
L.
,
Gearing
D. P.
,
White
L. S.
,
Comptom
D. L.
,
Schooley
K.
,
Donovan
P. J.
(
1994
)
Role of leukemia inhibitory factor and its receptor in mouse primordial germ cell growth.
Development
120
,
3145
3153
De Felici
M.
,
McLaren
A.
(
1983
)
In vitro culture of mouse primordial germ cells.
Exp. Cell. Res
144
,
417
427
De Felici
M.
,
Siracusa
G.
(
1982
)
Survival of isolated, fully grown mouse ovarian oocytes is strictly dependent on external Ca2+.
Dev. Biol
92
,
539
543
De Felici
M.
,
Dolci
S.
(
1989
)
In vitro adhesion of mouse fetal germ cells to extracellular matrix components.
Cell. Diff. Dev
26
,
87
96
De Felici
M.
,
Dolci
S.
(
1991
)
Leukemia inhibitory factor sustains the survival of mouse primordial germ cells cultured on TM4feeder layers.
Dev. Biol
147
,
281
284
De Felici
M.
,
Dolci
S.
,
Pesce
M.
(
1993
)
Proliferation of mouse primordial germ cells in vitro: a key role for cAMP.
Dev. Biol
157
,
277
280
De Felici
M.
,
Pesce
M.
(
1994
)
Growth factors in mouse primordial germ cell migration and proliferation.
Progr. Growth Factor Res
5
,
135
145
Deutsh
P. J.
,
Sun
Y.
(
1992
)
The 38-amino acid form of pituitary adenylate cyclase-activating polypeptide stimulates dual signaling cascades in PC12 cells and promotes neurite outgrowth.
J. Biol. Chem
267
,
5108
5113
Dolci
S.
,
Williams
D. E.
,
Ernst
M. K.
,
Resnick
J. L.
,
Brannan
C. L.
,
Fock
L. F.
,
Lyman
S. D.
,
Boswell
S. H.
,
Donovan
P. J.
(
1991
)
Requirement for mast cell growth factor for primordial germ cell survival in culture.
Nature
352
,
809
811
Dolci
S.
,
Pesce
M.
,
De Felici
M.
(
1993
)
Combined action of stem cell factor, leukemia inhibitory factor, and cAMP on in vitro proliferation of mouse primordial germ cells.
Mol. Reprod. Dev
35
,
134
139
Ferri
G. L.
,
Papadia
C.
,
Cocchia
D.
,
Polak
J. M.
(
1987
)
Aluminum foil moulds for cryostat blocks.
Stain Technol
62
,
59
60
Godin
I.
,
Deed
R.
,
Cooke
J.
,
Zsebo
K.
,
Dexter
M.
,
Wylie
C. C.
(
1991
)
Effects of steel gene product on mouse primordial germ cells in culture.
Nature
352
,
807
809
Gressens
P.
,
Hill
J. M.
,
Gozes
I.
,
Fridkin
M.
,
Brenneman
D.
(
1993
)
Growth factor function of vasoactive intestinal peptide in whole cultured mouse embryos.
Nature
362
,
155
158
Harper
J. F.
,
Brooker
G.
(
1976
)
Femtomole sensitive radioimmunoassay for cAMP and GMP after 2O-acetylation by acetic anhydride in aqueous solution.
J. Cyclic Nucleotide Res
1
,
207
218
Hashimoto
H.
,
Ishihara
T.
,
Shigemoto
R.
,
Mori
K.
,
Nagata
S.
(
1993
)
Molecular cloning and tissue distribution of a receptor for pituitary adenylate cyclase-activating polypeptide.
Neuron
11
,
333
342
Heindel
J. J.
,
Powell
C. J.
,
Paschell
C. S.
,
Arimura
A.
,
Culler
C. D.
(
1992
)
A novel hypothalamic peptide, pituitary adenylate cyclase activating peptide, modulates Sertoli cell function in vitro.
Biol. Reprod
47
,
800
806
Hirano
T.
,
Matsuda
T.
,
Nakajima
K.
(
1994
)
Signal trasduction through gp 130 that is shared among the receptors for the Interleukin 6 related cytokine subfamily.
Stem Cell
12
,
262
277
Hosoya
M.
,
Ondo
H.
,
Ogi
K.
,
Masuda
Y.
,
Miyamoto
Y.
,
Ohtaki
T.
,
Okazaki
H.
,
Arimura
A.
,
Fujino
M.
(
1993
)
Molecular cloning and functional expression of rat cDNAs encoding the receptor for pituitary adenylate cyclase activating polypeptide (PACAP).
Biochem. Biophys. Res. Commun
194
,
133
143
Jackson
T. R.
,
Blair
L. A. C.
,
Marshall
J.
,
Goedert
M.
,
Hanley
M. R.
(
1988
)
The mas oncogene encodes an angiotensin receptor.
Nature
335
,
437
439
Jaye
M.
,
Schlessinger
J.
,
Dionne
C. A.
(
1992
)
Fibroblast growth factor receptor tyrosine kinases: molecular analysis and signal transduction.
Bioch. Biophys. Acta
1135
,
185
199
Köwes
K.
,
Arimura
A.
,
Somogyvari-Vigh
A.
,
Vigh
S.
,
Miller
J.
(
1990
)
Immunohistochemical demonstration of a novel hypothalamic peptide, pituitary adenylate cyclase-activating plypeptide, in the ovine hypothalamus.
Endocrinology
127
,
264
271
Lowry
O.
,
Rosebrough
N.
,
Farr
A.
,
Randall
R. J.
(
1951
)
Protein measurement with the Folin phenol reagent.
J. Biol. Chem
193
,
265
275
McLean
I. W.
,
Nakane
P. K.
(
1974
)
Periodate-lysine-paraformaldehydefixative. a new fixative for immunoelectron microscopy.
J. Histochem. Cytochem
22
,
1077
1083
Miyata
A.
,
Arimura
A.
,
Dahl
R. R.
,
Minamino
N.
,
Uehara
A.
,
Jiang
L.
,
Culler
M.
,
Coy
D. H.
(
1989
)
Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells.
Biochem. Biophys. Res. Commun
164
,
567
574
Morrow
J. A.
,
Lutz
E. M.
,
West
K. M.
,
Fink
G.
,
Harmar
A. J.
(
1993
)
Cloning and expression of a cDNA encoding a receptor for pituitary adenyalte cyclase activating polypeptide (PACAP).
FEBS Lett
329
,
99
105
Pesce
M.
,
Farrace
M. G.
,
Dolci
S.
,
Piacentini
M.
,
De Felici
M.
(
1993
)
Stem cell factor and leukemia inhibitory factor promote primordial germ cell survival by suppressing programmed cell death (apoptosis).
Development
118
,
1089
1094
Pesce
M.
,
De Felici
M.
(
1995
)
Purification of mouse primordial germ cells by MiniMACS magnetic separation system.
Dev. Biol
170
,
722
725
Rossi
P.
,
Dolci
S.
,
Albanesi
C.
,
Grimaldi
P.
,
Geremia
R.
(
1993
)
Direct evidence that the mouse sex-determining gene Sry is expressed in the somatic cells of male fetal gonads and in the germ cell line in the adult testis.
Mol. Reprod. Dev
34
,
369
373
Sethi
T.
,
Rozengurt
E.
(
1991
)
Multiple neuropeptide stimulate clonal growth of small cell lung cancer: effect of bradykinin, vasopressin, cholocystokinin, galanin and neorotensin.
Cancer Res
51
,
3621
3623
Sethi
T.
,
Rozengurt
E.
(
1991
)
Galanin stimulates Ca2+mobilization, inositol phosphate accumulation and clonal growth in small cell lung cancer cells.
Cancer Res
51
,
1674
1679
Shivers
B. D.
,
Gorcs
T. J.
,
Gottschall
P. E.
,
Arimura
A.
(
1991
)
Two high affinity binding sites for pituitary adenylate cyclase-activating polypeptide have different tissue distribution.
Endocrinology
128
,
3055
3065
Shioda
S.
,
Legradi
G.
,
Leung
W.
,
Nakaio
S.
,
Nakaya
K.
,
Arimura
A.
(
1994
)
Localization of pituitary adenylate cyclase-activating polypeptide and its messenger ribonucleic acid in the rat testis by light and electron microscopic immunocytochemistry and in situ hybridization.
Endocrinology
135
,
818
825
Silen
M. L.
,
Gardner
J. D.
(
1993
)
Gastrointestinal peptides and cancer.
TEM
4
,
131
135
Spengler
D.
,
Waeber
C.
,
Pantaloni
C.
,
Holsboer
F.
,
Bockaert
J.
,
Seeburg
P. H.
,
Journot
L.
(
1993
)
Differential signal transduction by five splice variants of the PACAP receptor.
Nature
365
,
170
175
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