Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats
Evidence indicates that prolactin plays a crucial role in the normal function and development of the prostate, but abnormal high levels of the hormone are associated with hyperplasia and cancer of the gland. Aims: The present study was designed to describe the progressive specific histological abnor...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2015
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| Cite this: | Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats / D. Herrera-Covarrubias, G.A. Coria-Avila, X.P. Chavarra, C. Fernndez-Pomares, J. Manzo, G.E. Aranda-Abreu, M.E. Hernndez // Experimental Oncology. — 2015. — Т. 37, № 1. — С. 13-18. — Бібліогр.: 47 назв. — англ. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1859715016681324544 |
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| author | Herrera-Covarrubias, D. Coria-Avila, G.A. Chavarra, X.P. Fernndez-Pomares, C. Manzo, J. Aranda-Abreu, G.E. Hernndez, M.E. |
| author_facet | Herrera-Covarrubias, D. Coria-Avila, G.A. Chavarra, X.P. Fernndez-Pomares, C. Manzo, J. Aranda-Abreu, G.E. Hernndez, M.E. |
| citation_txt | Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats / D. Herrera-Covarrubias, G.A. Coria-Avila, X.P. Chavarra, C. Fernndez-Pomares, J. Manzo, G.E. Aranda-Abreu, M.E. Hernndez // Experimental Oncology. — 2015. — Т. 37, № 1. — С. 13-18. — Бібліогр.: 47 назв. — англ. |
| collection | DSpace DC |
| container_title | Experimental Oncology |
| description | Evidence indicates that prolactin plays a crucial role in the normal function and development of the prostate, but abnormal high levels of the hormone are associated with hyperplasia and cancer of the gland. Aims: The present study was designed to describe the progressive specific histological abnormalities in the prostate of rats with chronic hyperprolactinemia. Material and Methods: Prolactin was administered during 4; 12 or 24 weeks, and the resulting prostatic alterations were compared with control rats, and also with those treated with testosterone, or the combination of prolactin + testosterone. Results: Rats treated with prolactin, testosterone or prolactin + testosterone expressed precancerous histological abnormalities in the dorsolateral and ventral portions of the prostate as early as in 4 weeks of treatment, but in all cases the malignancy increased after 12 or 24 weeks of treatment. Conclusion: Our study confirms that chronic hyperprolactinemia is a cause of prostate precancerous pathologies. Key Words: prolactin, prostate, cancer, dysplasia, testosterone.
|
| first_indexed | 2025-12-01T08:11:41Z |
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Experimental Oncology 37, 13–18, 2015 (March) 13
LONG-TERM ADMINISTRATION OF PROLACTIN
OR TESTOSTERONE INDUCED SIMILAR PRECANCEROUS
PROSTATE LESIONS IN RATS
D. Herrera-Covarrubias1, *, G.A. Coria-Avila1, P. Chavarría Xicoténcatl2, C. Fernández-Pomares1,
J. Manzo1, G.E. Aranda-Abreu1, M.E. Hernández1
1Center for Brain Research, University of Veracruz, Xalapa, Ver. 91190, Mexico
2Faculty of Medicine, University of Veracruz, Xalapa, Ver. 91190, Mexico
Evidence indicates that prolactin plays a crucial role in the normal function and development of the prostate, but abnormal high
levels of the hormone are associated with hyperplasia and cancer of the gland. Aims: The present study was designed to describe
the progressive specific histological abnormalities in the prostate of rats with chronic hyperprolactinemia. Material and Methods:
Prolactin was administered during 4; 12 or 24 weeks, and the resulting prostatic alterations were compared with control rats, and
also with those treated with testosterone, or the combination of prolactin + testosterone. Results: Rats treated with prolactin,
testosterone or prolactin + testosterone expressed precancerous histological abnormalities in the dorsolateral and ventral portions
of the prostate as early as in 4 weeks of treatment, but in all cases the malignancy increased after 12 or 24 weeks of treatment.
Conclusion: Our study confirms that chronic hyperprolactinemia is a cause of prostate precancerous pathologies.
Key Words: prolactin, prostate, cancer, dysplasia, testosterone.
Among all types of tumors in men, prostate can-
cer (CaP) is the second most common worldwide
(≈ 15%) [1]. Every year, hundreds of thousands of new
cases of CaP are detected and up to 6.6% of them re-
sult in death [1]. The etiology of the disease is diverse,
and may include family history, age (> 65) [2], race
(> african-ancestry) [3], diet (> high-fat products) [4],
obesity (body mass index (BMI) > 25) [5], and bad
habits, such as smoking [6]. For that reason, treatments
are also diverse and may include surgery, radiation, che-
motherapy, vaccines, or hormone treatments. The latter
is mainly focused on the androgen deprivation therapy
(ADT), and it is perhaps, the first choice therapy [7].
The goal of ADT is to reduce the levels of androgens
that reach the prostate. ADT can slow down the growth
of the gland and may decrease its size. CaP has been
classically associated with androgens not only because
they induce cell division, but also because they are as-
sociated with spontaneous mutations that result in more
and abnormal cells within the gland [8, 9]. Paradoxically,
by the age of 65 the blood levels of androgens, i.e. tes-
tosterone (T) decrease by more than 50% as compared
to the levels observed at age 20 [10–13], and other hor-
mones such as prolactin (PRL) increase by at least 30%
above normal levels in elderly [14]. A similar shift in the
concentrations of those hormones is observed in studies
of the prostate of laboratory rats. For instance, treatment
with dopamine blockers results in a twofold increase
of serum PRL in males, but also results in a twofold de-
crease in T [15]. PRL has both direct and indirect effects
on the gland, and interacts with androgens in normal
and abnormal processes [16, 17]. In fact, CaP patients
express higher blood levels of PRL and less T [18],
as compared to healthy people of the same age [19–21].
Animal models and cell lines support the idea
that PRL, via its receptor (PRLR), activates the Jak2-
Stat5a/b pathway that may result in tumorige-
nesis [22]. So far, studies on laboratory rats have
shown that treatment with PRL results in enlargement
of the prostate [17, 23], suggesting that high levels
participate in the histological alterations in the gland.
However, the timed progression and the specific
histological alterations caused by high levels of PRL
during long periods have not been described yet. Thus,
in the present study we assessed the effects of treat-
ment with PRL during 4; 12 or 24 weeks on labora-
tory rats in comparison with treatment with T alone,
or PRL + T combination. We hypothesized that PRL
would induce prostatic precancerous lesions as severe
as those induced by T. In addition, we hypothesized
that PRL + T combination would induce more severe al-
terations than either of the two hormones given alone.
MATERIAL AND METHODS
Animals. Fifty-four Wistar male rats were used
(Rattus norvegicus albinus). They were purchased
from a certified animal supplier in Mexico (Rismart®)
and were 12 weeks old at the start of the study. The
rats were housed in large plexiglas cages (50 × 30 ×
20 cm), and kept in a colony room at the Center for
Brain Research, University of Veracruz in a 12–12 h re-
verse Light-Dark cycle (lights off at 8:00 h). Water and
commercial feed (Rismart® rat chow) were provided
ad libitum. All the experimental procedures were ap-
proved by an admission committee of the graduate
program in neuroetho logy, following the Official
Submitted: November 06, 2014
*Correspondence: Tel.: +52-228-8418900 EXT. 13609;
Fax: +52–228–8418900 EXT. 13611;
E-mail: dherrera@uv.mx
Abbreviations used: ADT — androgen deprivation therapy; AR — an-
drogen receptor; BPH — benign prostatic hyperplasia; BMI — body
mass index; CaP — prostate cancer; DLP — dorsolateral prostate;
DNA — desoxyribonucleic acid; i.p. — intraperitoneal; N:C —
nucleus:cytoplasm ratio; PRL — prolactin; PRLR — prolactin recep-
tor; s.c. — subcutaneous; T — testosterone; VP — ventral prostate.
Exp Oncol 2015
37, 1, 13–18
ORIGINAL CONTRIBUTIONS
14 Experimental Oncology 37, 13–18, 2015 (March)
Mexican Norm NOM-062-ZOO-1999 for use and care
of laboratory animals.
Hormone treatments. Rats were randomly
organized in 5 groups, depending on the hormone
treatment they received. 1) The PRL group received
intraperitoneal (i.p.) injections of ovine PRL (SIGMA®),
of a dose of 1.7 IU diluted in 100 ml of injectable grade
water, equivalent to 50 μg/100 ml of PRL every 12 h.
2) The T group received a subcutaneous (s.c.) silastic
implant in the back (Dow Corning Corp®. 062X0125 ID);
filled with T propionate (100 mg/kg of body weight).
The implant allowed the T propionate (T) to be con-
stantly released, which maintained high plasma levels
of the hormone as previously shown [24]. 3) The PRL
+ T group received both treatments. 4). The control
group was injected with saline solution (0.9%) 100 μl,
i.p. every 12 h, and received an empty s.c. implant
in the back. 5) The intact group comprised the animals
that received no treatment, but were handled during
the same time as experimental animals. Each group was
further divided in 3 subgroups, depending on the num-
ber of weeks they received treatment (4; 12, or 24).
Prostate samples and histology. One day after
the end of hormone treatment of each group, the rats
were deeply anesthetized with sodium pentobarbital
(35 mg/kg i.p.). Then, the accessory sexual organs
were carefully removed and placed into a container with
isotonic saline solution. Anesthetized rats were then
sacrificed with a second overdose of pentobarbital.
The prostate was identified under a dissecting micro-
scope (MEJI, EMZ-TR®), and was further divided into
ventral (VP) and dorsolateral (DLP) portions. The VP and
DLP were immersed in formol 10% during 24 h, then
dehydrated in alcohol 70% and 80% (1 h each), 95%
(3×2 h each), and ethanol 100% overnight, and two
more changes (1 h each) the following day, and finally
in xylene (3×1 h each). The tissue was then embedded
in paraffin wax 2×2 h each), sliced (5 µm thick) with
a microtome (RM 2125RT Leica®), mounted on slides
in a bath at 52 °C (containing pork skin-based gelatin
2.5 mg/100 ml) and then processed for Hematoxylin-
Eosin dye technique as follows: 1 h at 57 °C, deparaf-
finization in xylene (3×5 min each), rehydrated in alco-
hol/xylene (1:1) 5 min, ethanol 96% 3 min, hematoxylin
(10 min), water (30 s), acid alcohol (quick immersion),
water (10 s), lithium carbonate (30 s), water (10 s),
and eosin (4 quick immersions). Dehydration occurred
in ethanol 96% (3 min), ethanol 100% (2 min), ethanol/
xylene 1:1 (2 min), and xylene (5 min). Then, permount
was added and slides were coverslipped, air dried, and
observed under a light microscope (Olympus Ax70).
Photomicrographs were taken at × 40 magnification
and analyzed by the same experimenter (DH).
RESULTS
A thorough analysis did not demonstrate any histo-
logical abnormalities in rats from groups 4 and 5 (con-
trol and intact, respectively) after 4; 12 or 24 weeks.
In the DLP of intact rats the epithelium was cubic, ho-
mogeneous in size, with scarce papillae. The interstitial
space was homogeneous and contained collagen-
like eosinophilic reticular areas. The cell nuclei were
homogeneous in size, had a polar position towards
the base with a nucleus-cytoplasm ratio (N:C) of 1:4,
and chromatins were homogeneous and dispersed.
The myoepithelium was euplasic and the pattern
observed at low magnification was tubular (Fig. 1, a,
e, i and Table 1). The VP of intact rats was also normal
at 4; 12 or 24 weeks of observation. The epithelium was
columnar, homogeneous in size, and formed scarce
papillae. The interstitial space was homogeneous and
contained collagen-like eosinophilic reticular areas.
Nuclei were homogeneous in size, with a polar posi-
tion location towards the base, with a N:C ratio of 1:4,
and the chromatins were homogeneous. The myoepi-
thelium was euplasic and the pattern observed at low
magnification was tubular (Fig. 2, a, e, i and Table 2).
Unlike the rats from the intact or control groups, those
treated with PRL, T or PRL + T displayed histological
abnormalities in the DLP and VP as early as in 4 weeks
of treatment, but the degree of malignancy in the le-
sions increased after 12 or 24 weeks. For instance, after
4 weeks of treatment with PRL alone, the epithelium
of the DLP was not longer cubic, but columnar (meta-
plasic). There was hyperthrophy and hyperplasia, the
interstitial space was not longer observable, but was
rather compressed, and the cell nuclei were heteroge-
neous in size (anisokaryiosis) [25, 26]. Other features
such as myoepithelium, pattern, lumen content and
chromatin were apparently normal at 4 weeks of treat-
ment, but were abnormal after 12 or 24 weeks. Specifi-
cally, after 12 or 24 weeks of treatment with PRL alone
the epithelium showed dysplasia, there were many
papillae, the interstice contained many mononuclear
cells, there was anisokaryosis, the nuclei were not longer
polar, the N:C ratio was abnormal 1:1, the chromatin was
compact, and the myoepithelim was proplastic (Fig. 1,
b, f, j and see Table 1). In the VP similar abnormalities were
observed after 12 weeks of PRL (Fig. 2, b, f, j and see Table 2).
The effects of treatment with T were identified ahead of those
induced by PRL treatment. For example, with only four weeks
of treatment rats that received T or PRL + T expressed more
severe histological alterations than both the DLP and VP rats
treated with PRL alone. The epithelium showed dysplasia
(with T) or severe dysplasia (with PRL + T) within the first
month. In addition, the N:C ratio was 1:1 in T or PRL +
T groups, and the polarity of the nucleus was completely
lost. Altogether, these data indicate that PRL alone was
sufficient to induce precancerous alterations in the pros-
tate of rats. The lesions were similar to those caused
by T alone at 12 or 24 weeks, but the latter induced more
alterations during the first 4 weeks. In addition, the com-
bination of PRL + T increased the degree of malignancy,
even after 4 weeks of treatment (Fig. 1, c, d, g, h, k, l and
2, c, d, g, h, k, l).
DISCUSSION
Normal levels of PRL contribute to the growth and
functioning of the prostate [27]. PRL and its recep-
tor (PRLR) are present in the gland during both fetal
Experimental Oncology 37, 13–18, 2015 (March) 15
development and adulthood [22, 28–30], and they
are needed to maintain a normal weight and func-
tions of the prostate. In one study with pup rats the
low levels of PRL (reduced with injections of a rabbit
anti-rat PRL serum) resulted in significant reduction
of the weights of the prostate and seminal vesicles
[31]. By contrast, abnormal high PRL levels result
in an enlargement of the prostate [17, 23, 24, 32].
Earlier we have reported that prostate enlarges in rats
when PRL in blood during two continuous weeks
Intact
4
we
ek
s
12
w
ee
ks
24
w
ee
ks
Prolactin Testosterone Prolactin + Testosterone
Fig. 1. Dorsolateral prostate (× 40). Rats were treated during 4; 12 or 24 weeks with prolactin (PRL), testosterone (T), both (PRL + T),
or served as controls. Histological abnormalities were observed as early as 4 weeks of treatment (see Table 1 for details). Bar indicates 50 μm
Table 1. Dorsolateral prostate
Dorsal-later-
al prostate
4 weeks 12 weeks 24 weeks
Intact PRL T PRL + T Intact PRL T PRL + T Intact PRL T PRL + T
Epithelium
Form cubic columnar dysplasia Severe
dysplasia
cubic dysplasia dysplasia severe
dysplasia
cubic dysplasia dysplasia severe
dysplasia
Size even HT, HP anisocy-
tosis
anisocy-
tosis
even HT, HP anisocy-
tosis
anisocy-
tosis
even HT, HP anisocy-
tosis
anisocy-
tosis
Papillae scarce few few few few few few many few many many many
Interstice
Space even com-
pressed
com-
pressed
com-
pressed
even com-
pressed
com-
pressed
com-
pressed
even com-
pressed
com-
pressed
com-
pressed
Content collagen-
like
collagen-
like
collagen-
like
collagen-
like
collagen-
like
mononu-
clear cells
mononu-
clear cells
mononu-
clear cells
collagen-
like
mononu-
clear cells
mononu-
clear cells
mononu-
clear
cells
Nucleus
Size even aniso-
karyosis
aniso-
karyosis
aniso-
karyosis
even anisokary-
osis
anisokary-
osis
anisokary-
osis
even anisokary-
osis
anisokary-
osis
anisokary-
osis
Location polar polar no polar no polar polar no polar no polar no polar polar no polar no polar no polar
N:C ratio 1:4 1:4 1:1 1:1 1:4 1:1 1:1 1:1 1:1 1:1 1:1 1:1
Myoepithelim euplasia euplasia proplasia proplasia euplasia proplasia proplasia proplasia euplasia proplasia proplasia proplasia
Pattern (4X) tubular tubular tubular cribriform tubular tubular/
cribriform
tubular amorphous tubular tubular/
cribriform
amorphous amorphous
Lumen
Content amor-
phous
amor-
phous
amor-
phous
amor-
phous
amor-
phous
amorphous nothing nothing amor-
phous
nothing nothing nothing
Chromatin dispersed dispersed compact compact dispersed compact compact compact dispersed compact compact compact
Rats were treated during 4; 12 or 24 weeks with prolactin (PRL), testosterone (T), both (PRL + T), or served as controls. Histological abnormalities were ob-
served as early as to 4 weeks of treatment. HT = hypertrophy, HP = hyperplasia. Nucleus-Cytoplasm ratio (N:C).
16 Experimental Oncology 37, 13–18, 2015 (March)
reaches chronic steady levels of about 40 ng/ml [33]
exceeding only by 5% the normal highest PRL levels
expressed in every circadian cycle (12–38 ng/ml) [24].
Human patients with benign prostatic hyperplasia
(BPH) have higher blood levels of PRL, and the same
occurs in patients with CaP [21]. Prostate may not
depend on pituitary PRL for its growth since the gland
itself can produce PRL by its secretory epithelium
[29]. Furthermore, high levels of PRL are also found
in obese individuals, suggesting that the adipose tis-
sue itself may function as an endocrine organ [34–36].
Interestingly, the expression of PRLR is reduced
Table 2. Ventral prostate
Ventral pros-
tate
4 weeks 12 weeks 24 weeks
Intact PRL T PRL + T Intact PRL T PRL + T Intact PRL T PRL + T
Epithelium
Form columnar columnar dysplasia dysplasia columnar dysplasia dysplasia dysplasia columnar dysplasia dysplasia severe
dysplasia
Size even HT, HP anisocy-
tosis
anisocy-
tosis
even HT, HP anisocy-
tosis
anisocy-
tosis
even HT, HP anisocy-
tosis
anisocy-
tosis
Papillae scarce few few few few few few many few many many many
Interstice
Space even com-
pressed
com-
pressed
com-
pressed
even com-
pressed
com-
pressed
com-
pressed
even com-
pressed
com-
pressed
com-
pressed
Content collagen-
like
collagen-
like
collagen-
like
collagen-
like
collagen-
like
mononu-
clear cells
mononu-
clear cells
mononu-
clear cells
collagen-
like
mononu-
clear cells
mononu-
clear cells
mononu-
clear cells
Nucleus
Size even aniso-
karyosis
aniso-
karyosis
aniso-
karyosis
even anisokary-
osis
anisokary-
osis
anisokary-
osis
even anisokary-
osis
anisokary-
osis
anisokary-
osis
Location polar polar no polar no polar polar polar no polar no polar polar no polar no polar no polar
N:C ratio 1:4 1:4 1:1 1:1 1:4 1:1 1:1 1:1 1:1 1:1 1:1 1:1
Myoepithelim euplasia euplasia proplasia proplasia euplasia proplasia proplasia proplasia euplasia proplasia proplasia euplasia
Pattern (4X) tubular tubular tubular cribriform tubular tubular/
cribriform
tubular amorphous tubular tubular/
cribriform
amorphous amorphous
Lumen
Content amor-
phous
amor-
phous
amor-
phous
amor-
phous
amor-
phous
amorphous nothing nothing amor-
phous
nothing nothing nothing
Chromatin dispersed dispersed compact compact dispersed compact compact compact dispersed compact compact compact
Rats were treated during 4; 12 or 24 weeks with prolactin (PRL), testosterone (T), both (PRL+T), or served as controls. Histological abnormalities were ob-
served as early as to 4 weeks of treatment. HT = hypertrophy, HP = hyperplasia. Nucleus-Cytoplasm ratio (N:C).
4
we
ek
s
12
w
ee
ks
24
w
ee
ks
Intact Prolactin Testosterone Prolactin + Testosterone
Fig. 2. Ventral prostate (×40). Rats were treated during 4; 12 or 24 weeks with prolactin (PRL), testosterone (T), both (PRL+T), or served
as controls. Histological abnormalities were observed as early as 4 weeks of treatment (see Table 2 for details). Bar indicates 50 μm
Experimental Oncology 37, 13–18, 2015 (March) 17
in prostate of the patients with the high grade cancer
(>4 in Gleason scale) [28]. However, it has been ar-
gued that such reduction of PRLR may be associated
with the presence of poorly differentiated prostatic
cells, which express less PRLR [28].
Our results indicate that in rats, high levels of PRL
during periods of 4 weeks or more result in histological
alterations of the prostate that may be considered as pre-
cancerous. The PRL-induced lesions are very similar
to those induced by T alone, but the combination of both
hormones results in more severe histological alterations
after 4 weeks. Anysokaryosis, polarity and alterations
in N:C ratio indicate the changes in chromosome orga-
nization, which in turn can affect gene expression [37]
resulting in dysplasia. In addition, the myoepithelium
was proplastic, and the chromatin was compact, which
indicate that both hormone treatments did activate cell
division. In addition, the presence of mononuclear cells
in the interstice and the absence of the luminal content
(see Tables 1, 2), suggest the activation of inflammation
mechanisms as well. The combination of PRL + T resulted
in similar, but more severe alterations. These results also
indicate a synergistic effect of two hormones in the de-
velopment of prostate pathology.
Therefore, according to the present study and
others [22, 38–40], individuals with chronic high levels
of PRL for 4 weeks or more may express abnormal
precancerous histological features in the prostate.
Altogether, the data support the idea that regardless
of the source of PRL (e.g. systemic, pituitary, prostatic,
or adipose) it may be responsible of histological al-
terations of the prostate that may become precancer-
ous, even in individuals with low levels of androgens.
In the last decade, some preclinical trials have also
contri buted to understanding the positive effect of anti-
PRL treatment on CaP [41–44]. However, better out-
comes have been found with the combined suppression
of androgens and PRL together [45]. Further research
is needed to understand the specific role of these hor-
mones in the development and maintenance of prostate
pathologies including cancer [46, 47].
ACKNOWLEDGMENTS
This study was supported by the Mexican Coun-
cil for Science and Technology (CONACyT) to DHC
(No. 35258), to MEHA (No. 106531) and by academic
group UV-CA-304 (Neuroquímica) from the Center for
Brain Research, University of Veracruz. The authors want
to give special thanks to MVZ Esp. Juan Rosales Raya for
his assistance with the histological descriptions.
CONFLICTS OF INTEREST
The authors declare that they have no conflict
of interest.
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Copyright © Experimental Oncology, 2015
|
| id | nasplib_isofts_kiev_ua-123456789-145448 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 1812-9269 |
| language | English |
| last_indexed | 2025-12-01T08:11:41Z |
| publishDate | 2015 |
| publisher | Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| record_format | dspace |
| spelling | Herrera-Covarrubias, D. Coria-Avila, G.A. Chavarra, X.P. Fernndez-Pomares, C. Manzo, J. Aranda-Abreu, G.E. Hernndez, M.E. 2019-01-21T21:22:09Z 2019-01-21T21:22:09Z 2015 Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats / D. Herrera-Covarrubias, G.A. Coria-Avila, X.P. Chavarra, C. Fernndez-Pomares, J. Manzo, G.E. Aranda-Abreu, M.E. Hernndez // Experimental Oncology. — 2015. — Т. 37, № 1. — С. 13-18. — Бібліогр.: 47 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/145448 Evidence indicates that prolactin plays a crucial role in the normal function and development of the prostate, but abnormal high levels of the hormone are associated with hyperplasia and cancer of the gland. Aims: The present study was designed to describe the progressive specific histological abnormalities in the prostate of rats with chronic hyperprolactinemia. Material and Methods: Prolactin was administered during 4; 12 or 24 weeks, and the resulting prostatic alterations were compared with control rats, and also with those treated with testosterone, or the combination of prolactin + testosterone. Results: Rats treated with prolactin, testosterone or prolactin + testosterone expressed precancerous histological abnormalities in the dorsolateral and ventral portions of the prostate as early as in 4 weeks of treatment, but in all cases the malignancy increased after 12 or 24 weeks of treatment. Conclusion: Our study confirms that chronic hyperprolactinemia is a cause of prostate precancerous pathologies. Key Words: prolactin, prostate, cancer, dysplasia, testosterone. This study was supported by the Mexican Council for Science and Technology (CONACyT) to DHC (No. 35258), to MEHA (No. 106531) and by academic group UV-CA-304 (Neuroquímica) from the Center for Brain Research, University of Veracruz. The authors want to give special thanks to MVZ Esp. Juan Rosales Raya for his assistance with the histological descriptions. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats Article published earlier |
| spellingShingle | Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats Herrera-Covarrubias, D. Coria-Avila, G.A. Chavarra, X.P. Fernndez-Pomares, C. Manzo, J. Aranda-Abreu, G.E. Hernndez, M.E. Original contributions |
| title | Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats |
| title_full | Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats |
| title_fullStr | Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats |
| title_full_unstemmed | Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats |
| title_short | Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats |
| title_sort | long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats |
| topic | Original contributions |
| topic_facet | Original contributions |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/145448 |
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