Odgovor hipotalamo-hipofiznog sistema pacova na izoflavone soje : morfofunkcionalna studija
Effects of soy isoflavones on the hypothalamic-pituitary system in rats: a morphofunctional study
2012
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Authors:
Trifunović, SvetlanaContributors
Koko, VesnaManojlović-Stojanoski, Milica
Milošević, Verica
Šošić-Jurjević, Branka
Ajdžanović, Vladimir
Document Type:
Doctoral thesis (Published version)
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Show full item recordAbstract:
The soy isoflavones genistein and daidzein are being used increasingly as
preventive or alternative therapeutics in various pathological conditions. The effects of
soy isoflavones on the neuroendocrine system were, and still are, the subject of
numerous studies. Literature data predominantly focus on their effects on the
gonadotrophic axis, considering the soy isoflavones established estrogenic and
antiestrogenic mode of action. However, data about their potential effects on the
somatotrophic and adrenocorticotrophic systems are rather scarce, but nevertheless very
meaningful, considering the importance of these systems for the normal development
and function of an organism. Furthermore, in vitro studies provide only limited data,
that cannot be fully extrapolated to in vivo conditions.
The aim of this study was to investigate the effects of chronically applied
estradiol dipropionate, genistein and daidzein on the histological, stereological and
biochemical parameters of somatotrophic and adrenocorticotrophic systems in
orchidectomized adult rats.
Initially, adult (three months old) Wistar rats were divided into two groups:
sham operated (Sham) and orchidectomized (Orx). Two weeks after the surgery, the rats
were subdivided into seven experimental groups. The first group (Sham1) included
sham operated rats subcutaneously (s.c.) treated with an adequate volume of sterile olive
oil, the medium for estradiol dipropionate (medium I). In the second group (Orx1) were
orchidectomized rats s.c. treated with an adequate volume of medium I. The third group
(Orx1+E) was comprised of orchidectomized rats s.c. treated with estradiol dipropionate
in medium I (0.6 mg/kg b.w.). The fourth (sham operated – Sham2) and fifth
(orchidectomized – Orx2) group of rats were s.c. treated with adequate volumes of
absolute ethanol and sterile olive oil mixture, the medium for genistein or daidzein
(mixing ratio was 1:2; medium II). In the sixth group (Orx2+G) were orchidectomized
rats s.c. treated with genistein in medium II (30 mg/kg b.w.), while the seventh group
(Orx2+D) included orchidectomized rats s.c. treated with daidzein in the same medium
(30 mg/kg b.w.). All the groups of animals received the treatment during three weeks
(chronic treatment), and were sacrificed 24 h after the last injected dose. All the animals
were weighed before and after the treatment, while the pituitary weights were measured
after sacrificing. For the localization of arcuate (Arc), periventricular (Pe) and
paraventricular (PVN) nuclei, as well as for median eminence (ME) cresyl violet
histochemical staining was used. Hypothalamic releasing hormones (growth hormone
releasing hormone – GHRH, somatostatin – SS, corticotrophin releasing hormone –
CRH) and pituitary cells (somatotrophic – GH and adrenocorticotrophic – ACTH) were
immunohistochemically (peroxidase-antiperoxidase) labeled. Histochemically stained
and immunohistochemically labeled hypothalamic sections, as well as
immunohistochemically labeled pituitary sections were stereologically analysed, using
newCast stereological software package. The following values were obtained: the Arc,
Pe and PVN nuclei volumes, volume density of SS neurones, volumes of the pituitaries,
the volume and numerical density of GH and ACTH cells, as well as the absolute
numbers and volumes of GH and ACTH cells. The circulating GH and ACTH were
determined biochemically. The obtained data were statistically processed.
Orchidectomy significantly (p<0.05) decreased the body weight of adult rats in
comparison to Sham1 operated group. Chronic treatment with estradiol dipropionate
caused a significant (p<0.05) decrease in body weight compared to the Orx1 group of
rats. There were no changes in the same parameter after chronic treatments with
genistein or daidzein, in comparison to Orx2 group. Orchidectomy of adult rats led to a
decrease (p<0.05) in absolute pituitary weight, while the pituitary volume remained
unchanged compared to Sham1 group. Treatment with estradiol dipropionate increased
(p<0.05) absolute pituitary weight and volume, in comparison to Orx1 group of rats.
Genistein treatment increased (p<0.05) absolute pituitary weight and volume compared
to Orx2 group, while the same parameters remained unchanged after daidzein treatment.
Orchidectomy provoked a statistically significant enlargement (p<0.05) of the
Arc nucleus volume; a decrease (p<0.05) of: the GHRH and SS amounts in ME, the
volume density of SS neurons in Pe nucleus, the volume and numerical density of GH
cells, while orchidectomy did not affect: the volume of Pe nucleus, the absolute number,
volume and intensity of staining of GH cells and GH level in blood, all corresponding to
the appropriate parameters of Sham group. Administration of estradiol dipropionate to
orchidectomized rats provoked an enhancement (p<0.05) of: Arc and Pe nucleus
volume, the volume density of SS neurons in Pe nucleus, the SS amount in ME, the
intensity of staining of GH cells and GH level in blood; and a decrease (p<0.05) of the
volume and numerical density of GH cells; while the treatment did not affect: the
GHRH amount in ME, the absolute number and volume of GH cells, all corresponding
to the appropriate parameters of Orx group. Genistein treatment caused an increase
(p<0.05) in: Arc nucleus volume, the GHRH and SS amounts in ME, the volume
density of SS neurons in Pe nucleus, the volume and numerical density of GH cells, the
absolute number and intensity of staining of GH cells, GH level in blood; while the
treatment did not affect: the Pe nucleus volume and volume of GH cells, all
corresponding to the appropriate parameters of Orx group. Daidzein treatment caused an
increase (p<0.05) in: the GHRH amount in ME, the volume density of GH cells, volume
and intensity of staining of GH cells; and a decrease (p<0.05) of: numerical density and
absolute number of GH cells, while the treatment did not affect: Arc and Pe nucleus
volume, the volume density of SS neurons in Pe nucleus, the SS amount in ME and GH
level in blood, all corresponding to the appropriate parameters of Orx group.
Orchidectomy provoked a statistically significant enlargement (p<0.05) of: the
PVN volume, the volume density of CRH and CRH/cFos neurons in PVN, the CRH
amount in ME and ACTH level in blood; a decrease (p<0.05) of: the volume and
numerical density and intensity of staining of ACTH cells; while the treatment did not
affect the absolute number and volume of ACTH cells, all corresponding to the
appropriate parameters of Sham group. Administration of estradiol dipropionate to
orchidectomized rats provoked an enhancement (p<0.05) of: the volume density of
CRH/cFos neurons in PVN, the CRH amounts in ME, the number of ACTH cells and
ACTH level in blood; a decrease (p<0.05) of : the volume and numerical density and
intensity of staining of ACTH cells; while the treatment did not affect: PVN volume, the
volume density of CRH neurons in PVN and volume of ACTH cells, all corresponding
to the appropriate parameters of Orx group. The treatment with genistein caused an
increase (p<0.05) in: the volume density of CRH/cFos neurons in PVN, the volume
density and absolute number of ACTH cells and ACTH level in blood; a decrease
(p<0.05) of: the numerical density and intensity of staining of ACTH cells; while the
treatment did not affect: PVN volume, the volume density of CRH neurons in PVN, the
CRH amounts in ME and volume of ACTH cells, all corresponding to the appropriate
parameters of Orx group. Daidzein treatment caused an increase (p<0.05) in: the volume
density of CRH/cFos neurons in PVN and ACTH level in blood; a decrease (p<0.05) of
the volume density of CRH neurons in PVN; while the treatment did not affect: PVN
volume, the CRH amounts in ME, the stereological parameters of ACTH cells, all
corresponding to the appropriate parameters of Orx group.
These results indicate stimulatory effects of genistein on the majority of
examined histological, stereological and biochemical parameters of the somatotropic
and adrenocorticotrophic systems, while daidzein has less pronounced stimulatory
effects on the examined parameters. This study represents a solid basis for some further
investigations aimed at establishing the precise mechanisms of genistein/daidzein
actions on the somatotropic and hypothalamic–pituitary–adrenal systems and their
potential therapeutic usefulness.
Keywords:
Genistein; Daidzein; GHRH; SS; GH cells; CRH; ACTH cellsSource:
University of Belgrade, Faculty of Biology, 2012, 1-183Funding / projects:
- The effects of select plant extracts, phytoestrogens, steroid and peptide hormones on the rat neuroendocrine system (RS-MESTD-Basic Research (BR or ON)-173009)
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http://nardus.mpn.gov.rs/123456789/2040
https://radar.ibiss.bg.ac.rs/handle/123456789/2426