Discrepancy between Prolactin (PRL)
Messenger Ribonucleic Acid and
PRL Content in Rat Fetal Pituitary
Cells: Possible Role of Dopamine
E. L. Hooghe-Peters, A. Belayew, P. Herregodts, B. Velkeniers,
G. Smets, J. A. Martial, and L. Vanhaelst
Department of Pharmacology (E.L.H-P., B.V., L.V.)
Pharmaceutical Institute (P.H.)
Department of Experimental Pathology (G.S.)
Medical School
Vrije Universiteit Brussel
B-1090 Brussels, Belgium
Genetic Engineering Laboratory (A.B., J.A.M.)
Universite de Liege
B-4000 Sart-Tilman, Belgium
Data are controversial concerning the time when
PRL-synthesizing cells are detected for the first time
in the rat pituitary. Using a very sensitive immuno-
cytochemical technique, we could visualize only a
few PRL cells before day 10 after birth. At that time,
pituitary PRL was still 200 times less abundant than
in the adult (on a tissue weight basis) whereas PRL
mRNA per mg total RNA was only 80 times lower
than in the adult. However, by in situ hybridization,
we could demonstrate the presence of PRL mRNA
in cells from fetal day 18 on. We have also followed
the expression of GH gene in rat pituitary cells during
development. In contrast to results obtained with
PRL cells, quantitative analysis of cDNA probe hy-
bridization to GH mRNA correlated well with meas-
urements of immunostained cells. We found that
PRL was released in the blood from fetal day 19
onwards. Thus, at that time PRL is synthesized and
secreted but not stored. We therefore measured
brain dopamine levels, and the data support the idea
that the rise in dopamine levels after birth contrib-
utes to PRL storage. We confirmed in vitro that
newborn pituitary cells can store PRL when cultured
in the presence of dopamine. (Molecular Endocri-
nology 2: 1163-1168,1988)
INTRODUCTION
The rat anterior pituitary gland contains at least six
distinct types of endocrine cells, expressing the follow-
ing hormones: ACTH, TSH, PRL, GH, FSH, and LH (1).
Attempts to trace the cell lineages and even the timing
0888-8809/88/1163-1168$02.00/0
Molecular Endocrinology
Copyright © 1988 by The Endocrine Society
of pituitary cell commitment is hampered by the com-
plexity of a small organ made of a large variety of cell
types. These cells divide and differentiate according to
separate schedules and are under the control of various
humoral (mainly neuroendocrine) and cellular (paracrine)
factors. In order to overcome some of these problems,
we have used the following strategy to monitor the
ontogeny of PRL- and GH-producing cells. We have
followed the expression of PRL and GH genes in rat
pituitary cells during development. Dissociated cells
were analyzed for their cytoplasmic mRNA content by
in situ hybridization and for hormone storage by im-
munoperoxidase cytochemistry. Quantitative analysis
of cDNA probe hybridization to GH mRNA correlated
well with measurements of immunostained cells. In
contrast there was a discrepancy between PRL mRNA
expression (high from fetal day 18) and PRL storage
(low until 10 days postnatal). Very few PRL immunore-
active cells could indeed be observed around birth.
These data were confirmed by analysis of PRL mRNA
and PRL extracted from adult vs. neonatal pituitaries.
However, by assaying PRL in the plasma we could
show that PRL was already released in the blood at
fetal days 19-21; after birth, plasma PRL concentration
dropped. One likely explanation was that PRL was
already synthesized in the cell but could not yet be
stored. It is suggested that dopamine (DA) is required
for storage. We observed that brain DA levels raise
after birth. In addition newborn pituitary cells can ac-
cumulate PRL when cultured in the presence of DA.
RESULTS
In a first approach, the developmental expression of
GH and PRL genes was studied in dissociated rat
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