NLM CIT. ID: 20182998
TITLE: Adenovirus-mediated herpes simplex virus type-1 thymidine kinase gene
therapy suppresses oestrogen-induced pituitary prolactinomas.
AUTHORS: Windeatt S; Southgate TD; Dewey RA; Bolognani F
Perone MJ; Larregina AT; Maleniak TC; Morris ID; Goya RG
Klatzmann D; Lowenstein PR; Castro MG
AUTHOR AFFILIATION:
Molecular Medicine and Gene Therapy Unit, School of Medicine,
University of Manchester, United Kingdom.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
EC 2.7.1.21 (Thymidine Kinase)
0 (Estrogens)
ABSTRACT:
We tested the hypothesis that gene transfer using recombinant
adenovirus vectors (RAds) expressing herpes simplex virus type 1
thymidine kinase (HSV1-TK) might offer an alternative therapeutic
approach for the treatment of pituitary prolactinomas that do not
respond to classical treatment strategies. HSV1-TK converts the
prodrug ganciclovir (GCV) to GCV monophosphate, which is in turn
further phosphorylated by cellular kinases to GCV triphosphate, which
is toxic to proliferating cells. One attractive feature of this
system is the bystander effect, whereby untransduced cells are also
killed. Our results show that RAd/HSV1-TK in the presence of GCV is
nontoxic for the normal anterior pituitary (AP) gland in vitro, but
causes cell death in the pituitary tumor cell lines GH3, a
PRL/GH-secreting cell line, and AtT20, a corticotrophic cell line. We
have used sulpiride- and oestrogen-induced lactotroph hyperplasia
within the rat AP gland as an in vivo animal model. Intrapituitary
infection of rats bearing oestrogen-induced lactotroph hyperplasia,
with RAd/ HSV1-TK and subsequent treatment with GCV, decreases plasma
PRL levels and reduces the mass of the pituitary gland. More so,
there were no deleterious effects on circulating levels of other AP
hormones, suggesting that the treatment was nontoxic to the AP gland
in situ. In summary, our results show that suicide gene therapy using
the HSV1-TK transgene could be further developed as a useful
treatment to complement current therapies for prolactinomas.
NLM PUBMED CIT. ID:
10720079
SOURCE: J Clin Endocrinol Metab 2000 Mar;85(3):1296-305
NLM CIT. ID: 20153930
TITLE: Pituitary prolactin-secreting tumor formation: recent developments [In
Process Citation]
AUTHORS: Xu RK; Wu XM; Di AK; Xu JN; Pang CS; Pang SF
AUTHOR AFFILIATION:
Department of Physiology, Institute of Basic Medical Sciences, Chinese
Academy of Preventive Medicine, Beijing, China.
LANGUAGES:
Eng
ABSTRACT:
Prolactinoma is the most common type of primary pituitary tumors. It
occurs more frequently in women than in men. Dopaminergic agonists
are effective in the shrinkage of prolactin-secreting pituitary tumor
and are preferred in some patients. However, pituitary radiotherapy
may enable the long-term removal of prolactin-secreting tumor cells.
Recent evidence suggests that prolactinoma is a heterogeneous
disorder with complicated and multifactorial etiology and
pathogenesis. Apparently, a thorough understanding of prolactinoma
tumorigenesis would be important. To facilitate investigations on
tumorigenesis of prolactinoma, animal models for prolactinomas have
been developed. These models have expedited our progress in the
recent years. Many researchers consider the F(344) rat to be the most
sensitive strain of rats to estrogen (E(2))-induced prolactinoma
formation. Nonetheless, E(2) treatment for 60 days also induces the
formation of pituitary prolactin-secreting adenoma in male
Sprague-Dawley (SD) rats. Evidently, the SD rat is also a good animal
for prolactinoma investigations. Following E(2) implantation,
prolactinomas developed in the eutopic adenohypophysis in situ and/or
ectopic pituitary grafted under the renal capsule in SD rats. These
observations favor the hypothesis that prolactinoma growth is the
result of pathological changes in the adenohypophysis and/or
hypothalamus. In the latter case, abnormal release of hypothalamic
dopamine, GABA, or brain-gut peptides (such as cholecystokinin,
vasoactive intestinal polypeptide, galanin, angiotensin, opioid
peptide, gastrin, gastrin-releasing peptide, pancreatic polypeptide,
and adrenocorticotropic hormone) results in some of the pathological
changes that may lead to hyperprolactinemia and/or prolactinoma
development. Dysregulation of prolactin synthesis and secretion may
be the result of prolactin gene modulation. In E(2)-induced rat
prolactinomas, prolactin mRNA contents and the expression of some
proto-oncogenes, e.g. c-myc and c-ras, TGFalpha and TGFbeta1 mRNA
were significantly changed. The above findings are consistent with
results in human prolactinoma development. In addition, in rats
abnormal expression of the prolactin gene was correlated with
hypomethylated status of CpG sites in exons 1, 2 and 4 of the
prolactin gene, as well as the increase in hypersensitive sites to
DNase 1 in the encoding region of the prolactin gene. In E(2)-treated
rats, a point mutation with a base substitution from cytidine (C) to
adenine (A) was found at the -36-bp site of the proximal promoter of
the prolactin gene in eutopic pituitary prolactinomas, but no change
was observed in the same sequence of the prolactin gene in ectopic
prolactinoma. The association of a base substitution with the
hyperexpression of the prolactin gene in eutopic prolactinomas
suggests that different mechanisms may mediate the formation of
eutopic and ectopic prolactin-secreting tumors. Melatonin decreases
the expression of the prolactin gene in vitro suggesting that this
pineal hormone may be a potential anticarcinogen in vivo. It has also
been shown that MT(2) (Mel(1b)) melatonin receptors are expressed in
anterior pituitary cells. The use of melatonin as a preventive or
therapeutic drug for prolactinomas should be further investigated. In
summary, improved knowledge on tumorigenesis of prolactinomas,
especially in the rat model, was noted. These E(2)-induced rat
prolactinoma models would facilitate future investigations, and
expected results shall be fruitful and exciting for the development
of future drug designs for the prevention and/or treatment of
prolactin-secreting pituitary tumors. Copyright 2000 S. Karger AG,
Basel
NLM PUBMED CIT. ID:
10686432
SOURCE: Biol Signals Recept 2000 Jan-Feb;9(1):1-20
[MEDLINE record in process]
UI - 20070581
AU - Yoshimura K; Tsuchida T; Kawamoto K
TI - Expression of cathepsin B and cystatin C in the human
adenohypophysis and in pituitary adenomas.
SO - Oncol Rep 2000 Jan-Feb;7(1):27-31
AD - Department of Neurosurgery, Kansai Medical University, Moriguchi,
Osaka 570, Japan.
The localization of cathepsin B, a potential promoter of prolactin (PRL)
release via extra renal renin-angiotensin system in the adenohypophysis,
and its inhibitor cystatin C in the human adenohypophysis and in
pituitary adenomas were examined using single and dual
immunohistochemical staining. In the adenohypophysis, cathepsin B was
expressed in about 50% of the ACTH-producing cells, and in 5% or less of
the GH- and PRL-producing cells. In contrast, cystatin C was expressed in
about 70% of the GH- and PRL-producing cells, but in only 5% or less of
the ACTH-producing cells. PRL-producing adenomas strongly expressed
cathepsin B, but only weakly expressed cystatin C, a pattern of staining
contrary to the expression in normal PRL-producing cells. The above
results suggest that cathepsin B may play a role in promoting PRL release
especially in PRL-producing adenomas.
NLM CIT. ID: 20066716
TITLE: Expression of prolactin-releasing peptide and its receptor messenger
ribonucleic acid in normal human pituitary and pituitary adenomas.
AUTHORS: Zhang X; Danila DC; Katai M; Swearingen B
Klibanski A
AUTHOR AFFILIATION:
Department of Medicine, Massachusetts General Hospital and Harvard
Medical School, Boston 02114, USA.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (prolactin-releasing peptide)
0 (receptor, prolactin-releasing peptide)
0 (Hypothalamic Hormones)
0 (Neuropeptides)
0 (Receptors, Neuropeptide)
0 (RNA, Messenger)
12629-01-5 (Somatropin)
GRANT/CONTRACT ID:
R01-DK-40947/DK/NIDDK
MH/NS 31862/MH/NIMH
ABSTRACT:
The recently identified PRL-releasing peptide (PrRP) is the first
hypothalamic peptide hormone that specifically stimulates PRL
production from the pituitary gland. Similar to other hypothalamic
regulatory hormones, it acts through its specific seven-transmembrane
domain, G protein-coupled receptor. Using RT-PCR, we examined
messenger ribonucleic acid (mRNA) expression of PrRP and its receptor
in normal human pituitary tissue and in pituitary tumors. PrRP mRNA
was expressed in all five normal pituitary glands examined. In
contrast, PrRP mRNA was detected in only 5 of 11 of the human
prolactinomas. All 5 prolactinomas expressing PrRP were responsive to
dopamine agonist treatment, whereas PrRP-negative prolactinomas were
non- or partially responsive. PrRP mRNA was also detected in 6 of 13
GH-secreting tumors and 5 of 10 clinically nonfunctioning tumors
investigated. PrRP receptor mRNA was found in all the normal and
neoplastic human pituitary samples studied. The production of PrRP
and its receptor by normal and neoplastic pituitary tissue raises the
question of whether it may regulate PRL production in an
autocrine/paracrine manner in pituitary tissue. Further investigation
of PrRP and its receptor expression and function will be needed to
clarify its potential role in regulating PRL secretion in normal
human lactotrophs and pituitary tumors.
NLM PUBMED CIT. ID:
10599733
SOURCE: J Clin Endocrinol Metab 1999 Dec;84(12):4652-5
UI - 99415649
AU - Hofland LJ; de Herder WW; Waaijers M; Zuijderwijk J; Uitterlinden P;
van Koetsveld PM; Lamberts SW
TI - Interferon-alpha-2a is a potent inhibitor of hormone secretion by
cultured human pituitary adenomas.
SO - J Clin Endocrinol Metab 1999 Sep;84(9):3336-43
AD - Department of Internal Medicine III, Erasmus University, Rotterdam,
The Netherlands. hofland@inw3.azr.nl
Interferon-alpha (IFN alpha) may exert direct inhibitory effects on cell
proliferation and on the production of different peptide hormones. We
investigated the effect of IFN alpha on hormone production by 15 GH-
secreting pituitary adenomas, 4 clinically nonfunctioning or gonadotroph
pituitary adenomas, and 4 prolactinomas in vitro. In the GH-secreting
pituitary adenoma cultures, a short term (72-h) incubation with IFN alpha
(50-100 U/mL) significantly inhibited GH secretion in 3 of 7 cases and
PRL secretion in 6 of 7 cultures. During prolonged incubation (14 days)
with IFN alpha, GH and/or PRL secretion was significantly inhibited in 7
of 8 cultures (GH, 17-78% inhibition; PRL, 39-88% inhibition). In the
clinically nonfunctioning or gonadotroph cultures, incubation with IFN
alpha resulted in inhibition of the secretion of gonadotropins and/or
alpha-subunit in all cases (27-62%), whereas in the prolactinoma cultures
PRL secretion was inhibited by IFN alpha in all cases (37-76%). The
effect of IFN alpha was additive to the inhibitory effects of the
dopamine agonist bromocriptine (10 nmol/L) or the somatostatin analog
octreotide (10 nmol/L). The inhibition of hormone secretion by IFN alpha
was accompanied by inhibition of the intracellular hormone
concentrations. The effect of IFN alpha was dose dependent, with an IC50
for inhibition of hormone secretion of 2.3 +/- 0.3 U/mL (n = 5), which is
relatively low compared with the concentrations that are reached in
patients treated with IFN alpha for various malignancies. In conclusion,
the potent antihormonal effect of IFN alpha on cultured pituitary
adenomas suggests that this drug might be of benefit in the treatment of
selected patients with secreting pituitary adenomas. As treatment with
IFN alpha is associated with considerable adverse reactions, studies with
this drug should only be considered in inoperable, invasive aggressive,
and dopamine agonist- and/or somatostatin analog-resistant functioning
pituitary macroadenomas.
NLM CIT. ID: 99145048
TITLE: Pituitary tumor transforming gene (PTTG) expression in pituitary
adenomas.
AUTHORS: Zhang X; Horwitz GA; Heaney AP; Nakashima M
Prezant TR; Bronstein MD; Melmed S
AUTHOR AFFILIATION:
Cedars-Sinai Research Institute-University of California School of
Medicine, Los Angeles 90048, USA.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Neoplasm Proteins)
0 (PTTG protein)
0 (RNA, Messenger)
12629-01-5 (Somatropin)
9002-60-2 (Corticotropin)
GRANT/CONTRACT ID:
DK 50238/DK/NIDDK
DK 7682/DK/NIDDK
ABSTRACT:
We recently cloned a novel pituitary tumor transforming gene (PTTG).
Here we report PTTG expression in human pituitary adenomas and in
normal pituitary tissue. In situ hybridization revealed PTTG
expression in nonfunctioning and in GH-secreting adenomas but not in
normal pituitary tissue. Using a more sensitive detection method,
RT-PCR, low level PTTG expression was detected in normal pituitary.
However, when expression levels in normal pituitary tissue were
compared with those in 54 pituitary tumors using comparative reverse
transcription polymerase chain reaction (RT-PCR), we found that most
tumor samples expressed higher levels of PTTG. More than 50% PTTG
increases were observed in 23 of 30 nonfunctioning pituitary tumors,
all 13 GH-producing tumors, 9 of 10 prolactinomas, and 1
ACTH-secreting tumor, with more than 10-fold increases evident in
some tumors. Furthermore, higher PTTG expression (P = 0.03) was
observed in hormone-secreting tumors that had invaded the sphenoid
bone (stages III and IV; 95% CI 3.118-9.715) compared with
hormone-secreting tumors that were confined to the pituitary fossa
(stages I and II; 95% CI 1.681-3.051). Therefore, PTTG abundance is a
molecular marker for invasiveness in hormone-secreting pituitary
tumors. The ubiquitous and prevalent expression of pituitary adenoma
PTTG suggests that PTTG plays a role in pituitary tumorigenesis and
invasiveness.
NLM PUBMED CIT. ID:
10022450
SOURCE: J Clin Endocrinol Metab 1999 Feb;84(2):761-7
NLM CIT. ID: 99187411
TITLE: Antiproliferative effects of melatonin and CGP 52608.
AUTHORS: Karasek M; Pawlikowski M
AUTHOR AFFILIATION:
Laboratory of Electron Microscopy, Chair of Pathomorphology, Medical
University of Lodz, Lodz, Poland. Micha.7497401@pharmanet.com.pl
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Antineoplastic Agents)
0 (Ligands)
0 (Receptors, Cytoplasmic and Nuclear)
0 (Thiazoles)
0 (Thiosemicarbazones)
73-31-4 (Melatonin)
87958-67-6 (CGP 52608)
ABSTRACT:
The antiproliferative effects of melatonin and CGP 52608, an exogenous
ligand for RZR/ROR receptors, are compared in the present paper. Both
compounds exerted similar inhibitory effects on the proliferation of
neoplastic cells in mouse colonic adenocarcinoma, DU 145 human
prostate cancer, MCF-7 human breast carcinoma, and rat
diethylstilbestrol-induced prolactinoma. Although it has been
suggested that melatonin may influence the proliferation of tumor
cells via RZR/ROR receptors, it cannot be excluded that the
antiproliferative effects of melatonin and CGP 52608 are unrelated
and mediated by different intracellular mechanisms.
NLM PUBMED CIT. ID:
10085466
SOURCE: Biol Signals Recept 1999 Jan-Apr;8(1-2):75-8
NLM CIT. ID: 99161941
TITLE: Vitamin E deficiency ataxia associated with adenoma.
AUTHORS: Benomar A; Yahyaoui M; Marzouki N; Birouk N
Bouslam N; Belaidi H; Amarti A; Ouazzani R; Chkili T
AUTHOR AFFILIATION:
Service de Neurologie (T. Chkili), Hopital des Specialites, CHU Ibn
Sina, Rabat-instituts, Morocco.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
1406-18-4 (Vitamin E)
9002-62-4 (Prolactin)
ABSTRACT:
Vitamin E is one of the most important lipid-soluble antioxidant
nutrient. Severe vitamin E deficiency (VED) can have a profound
effect on the central nervous system. VED causes ataxia and
peripheral neuropathy that resembles Friedreich's ataxia. We report
here a patient presenting this syndrome, but also a prolactin and FSH
adenoma. Both the neurological syndromes and the adenoma regressed
after treatment with alpha-tocopherol. Although, the presence of the
prolactinoma in this patient may not be related to his vitamin E
deficiency, alpha-tocopherol treatment seems to be beneficial and
might usefully be tested in patients with hypophyseal secreting other
forms of adenoma.
NLM PUBMED CIT. ID:
10064178
SOURCE: J Neurol Sci 1999 Jan 1;162(1):97-101
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