Correspondence
Estrogen receptor alpha to beta ratio:
A counterpart also in adrenal cortical neoplasia?
Dear Editor,
Estrogen receptors (ER) alpha and beta are well-
established counterparts of neoplasia in estro-
gen-responsive tissues, such as the breast or the
endometrium. In this context, the ER-alpha to
ER-beta balance (ratio) has been described as an
important predictor [1]. Interestingly however,
ERs have emerged as significant factors in neo-
plasms of other tissues, such as the pancreas,
the stomach and the liver.
Although the adrenal cortex is a major endocrine
organ, the studies that have been published till
now on its estrogen-mediated regulation have
focused on the actions of ERs in the central nervous
system (reviewed in [2]). Actions in the CNS subse-
quently and indirectly modulate the adrenal secre-
tion. Regarding direct in vivo modulation, only one
study in the human fetus has documented the
expression of ER-beta [3].
Apart from the scarcity of data concerning nor-
mal regulation, the physiological implication of
ERs in adrenal cortical adenomas and carcinomas
has not been systematically studied. To our knowl-
edge, adenoma remains an uninvestigated domain
and regarding carcinoma data come from two case
reports. One of them supports that ERs are unde-
tectable in pregnancy-associated adrenal cortical
carcinoma [4], and the other one suggests that
the expression is present, but at the same levels
as in the adjacent normal tissue [5].
The main point of the hypothesis is that ER-beta,
ER-alpha and the ER-beta/ER-alpha ratio may be
important predictors also in adrenal neoplasia,
irrespectively of pregnancy. Given the expression
in of ER-beta in the fetus, ER-beta may become
doi:10.1016/j.mehy.2007.12.006
How ethnicity affects risk of primary open-angle
glaucoma?
Dear Editor,
We read the paper by Weale [1] carefully in a re-
cent issue of Medical Hypotheses.
First, some established epidemiologic data do
not support the current hypothesis:
1225
particularly important during adrenal cortical
tumorigenesis and may indeed exhibit a regulatory
role, as the cells return to a dedifferentiated, ‘‘fe-
tal-like’’ status. At any case, this Letter points to
the need of ER-alpha and beta quantitative evalua-
tion in large series of adrenal cortical carcinomas,
which is to date absent in the literature.
References
[1] Shaaban AM, O’Neill PA, Davies MP, et al. Declining estro-
gen receptor-beta expression defines malignant progression
of human breast neoplasia. Am J Surg Pathol 2003;27:
1502–12.
[2] Bodo C, Rissman EF. New roles for estrogen receptor beta in
behavior and neuroendocrinology. Front Neuroendocrin
2006;27:217–32.
[3] Takeyama J, Suzuki T, Inoue S, et al. Expression and cellular
localization of estrogen receptors alpha and beta in the
human fetus. J Clin Endocrinol Metab 2001;86:2258–62.
[4] Fallo F, Pezzi V, Sonino N, Altavilla G, Barzon L. Adrenal
incidentaloma in pregnancy: clinical, molecular and immuno-
histochemical findings. J Endocrinol Invest 2005;28:459–63.
[5] Sanfilippo JS, Wittliff JL. Steroid hormone receptors in adrenal
cortical carcinoma. Am J Obstet Gynecol 1984;150: 326–7.
Despina Georgiadou*
Theodoros N. Sergentanis
George Papastratis
3rd Surgical Clinic,
‘‘George Gennimatas’’ General Hospital,
154, Mesogeion Avenue,
Athens 156 69, Greece
* Tel.: +30 2106546496; fax: +30 2107706915;
mobile: +30 6976435861
E-mail address: desangeor@yahoo.gr
(D. Georgiadou)
1. There are many evidences, which show that peo-
ples of the same place (same temperature),
have different risks for primary open angle glau-
coma (POAG). The first example is the preva-
lence of POAG between age-adjusted men and
women of the same place [2]. Second example
1226
is arising from the difference in the prevalence
of POAG between black and white adults in the
United States [3]. The third example is that at
regions with cold climates, older individuals
have lived in the cold weather for a longer time.
According to the hypothesis, they seem to have
more constricted superficial capillaries with
narrower lumens and lower predisposition to
glaucoma. Nevertheless, the risk for POAG
increases with age there [2].
2. Some investigators have compared the preva-
lence of glaucoma between African persons in
Africa and African-derived persons in the United
States [4]. They found remarkably similar preva-
lence of POAG between those two groups. In
other words, when African persons migrate from
Africa (warm climate) to United States (more
temperate climate); the prevalence of POAG
does not change remarkably.
3. Based on the hypothesis, at regions with more
temperate climates, superficial capillaries will
be constricted. Hence, the aqueous outflow
channels might dilate, and reduce a predisposi-
tion for POAG. In Europe (especially northern
places such as Norway, Sweden that are near
the North Pole) and the north of Canada, the
common pattern of glaucoma is POAG [4,2].
As we understand from the article’s title, the
author tries to explain ethnical differences in the
prevalence of glaucoma by different environmental
temperatures. We believe that 3-D configuration of
the eyeball which varies between different ethnic
groups and is related to genetic factors, lead to dif-
ferent magnitudes of the eye’s wall mechanical
stress and consequently different risks for glau-
coma [5].
doi:10.1016/j.mehy.2007.12.005
Exosomes: The Trojan horses of neurodegeneration
Exosomes are part of the family of ‘‘bioactive ves-
icles’’. Their role in bloodstream, where the distal
communication between cells is crucial, has been
extensively described in particular related to the
immune system activation. Exosomes secretion
can be used by cells – including neurons and
astrocytes [1] – to eject molecules destined for
lysosomal degradation. In addition, secreted exo-
somes are biologically active entities which are
important for the intercellular communication.
Correspondence
Acknowledgement
The authors thank Doctor Robert A. Weale (Eye
Department, University College London Hospital,
Euston Road, London WC1, United Kingdom) be-
cause of his permission to discuss about his pub-
lished article and for his honesty to respond some
of our questions and ambiguities about the article
by e-mail.
References
[1] Weale RA. Ethnicity and glaucoma: higher environmental
temperatures may accelerate the onset, and increase the
prevalence, of primary open-angle glaucoma. Med Hypoth-
eses 2007;69:432–7.
[2] Coleman A. Epidemiology of glaucoma. In: Morrison J,
Pollack I, editors. Glaucoma: science and practice. New
York: Thieme; 2003. p. 3–7.
[3] Friedman DS, Wolfs RC, O’Colmain BJ, Klein BE, Taylor HR,
West S. Prevalence of open-angle glaucoma among adults in
the United States. Arch Ophthalmol 2004;122:532–8.
[4] Buhrmann RR, Quigley HA, Barron Y, West SK, Oliva MS,
Mmbaga BBO. Prevalence of glaucoma in a rural east
African population. Invest Ophthalmol Vis Sci 2000;41:
40–8.
[5] Mehdizadeh AR, Hoseinzadeh A, Fazelzadeh A. What is
the real cause of glaucoma? Med Hypotheses 2007;69:
459–60.
Alireza Mehdizadeh
Amin Hoseinzadeh*
Afsoon Fazelzadeh
Mashad University of Medical Sciences (MUMS),
School of Medicine, Mashad, Iran
* Tel.: +98 9177075754; fax: +98 5118517505
E-mail address: hoseinzadeha831@mums.ac.ir
(A. Hoseinzadeh)
Exosomes from prion-infected neuronal cells
have been demonstrated to be efficient initiators
of prion propagation in uninfected recipient cells
and, more importantly, to produce prion disease
when inoculated into mice [2]. In Alzheimer dis-
ease (AD), b-amyloid peptides, that are intracellu-
larly generated, were shown to be released to the
extracellular space in association with exosomes
[3]. AD is characterized by a continuous loss of
neurons that are not replaced: why neurons die