Homeostasis ventral surface of the kidneys of bony

Homeostasis is regulated by
changes in the body’s internal and external environment. These triggers send
chemical messages throughout the body to specific glands that secrete hormones
that are required to carry out tasks to balance homeostasis. Some hormones are
needed for heat regulation, water regulation and glucose regulation. Others are
needed for balances in…. All hormones play an important role in the balance of
overall homeostasis (regulation, target cells, feedback loops). In particular, calcium
and phosphate homeostasis is controlled by shifts of calcium and phosphate
among five different compartments: 1. the extracellular fluids (ECF); 2. the
intracellular pool, itself divided into several compartments; 3. the bone and
the bone fluids; 4. the intestinal lumen; and 5. the renal tubular fluid (andre
b borle). Stanniocalcin (STC; previously named hypocalcin or teleocalcin) is a
glycoprotein hormone that was thought to be unique to teleostean and holostean
fish (KENICHI ISHIBASHI). Stanniocalcin is a group of hormones that’s main role
is to regulate calcium and phosphate. More recently, a human gene encoding the
second stanniocalcin-like protein, STC2, was identified. (KENICHI ISHIBASHI).

The role of stanniocalcin will be explained in more detail including
comparisons of the hormone in bony fish and new studies including STC2 in
mammals.

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The
corpuscles of Stannius

The
corpuscles of Stannius (CS) are small endocrine glands that are generally
located on the ventral surface of the kidneys of bony fishes (see fig. 1). They synthesize and
secrete stanniocalcin (STC) (molecular and cellular endocrinology). Initially, the glands were mistakenly
believed to be the piscine equivalents of mammalian adrenal glands due to their
intimate anatomical association with kidneys (evolution and roles of
stanniocalcin B.H.Y. Yeung, A.Y.S. Law, Chris K.C. Wong). Human STC was found to contain 273 amino acids in a 73%
sequence of similarity with fish STC (the
american journal of pathology). More recent studies comparing fish STC and
human STC suggest that certain human or mammalian STC has similar effects in
bony fish to its original form of STC. other studies suggest that human STC is
secreted and used differently compared to fish STC. strong signals of human STC
have been found in the ovaries, prostate and thyroid. Fish STC is secreted from
the corpuscles of Stannius and used primarily to protect against hypercalcemia
and regulation of calcium homeostasis. Due to their sequence similarity, many
studies have been conducted by administering either fish STC or human/mammalian
STC and focusing on how the hormone reacts and whether or not it has a similar
effect compared to the original form.

Stanniocalcin
in bony fish

The primary function of STC in
fish is to prevent hypercalcemia, and a rise in serum calcium levels is the
primary stimulus for secretion (Stanniocalcin: a novel protein regulating
calcium and phosphate transport across mammalian intestine) It begins with
osmoregulation. In bony fish, the primary organs for osmoregulation are the
gills or the intestines as the kidneys can’t secrete hypertonic urine. Unlike
terrestrial mammals, fish face the challenging task of balancing the dramatic
ionic/osmotic gradients between the aquatic environment and their body fluids (OSMOREGULATION
IN ZEBRAFISH: ION TRANSPORT MECHANISMS AND FUNCTIONAL REGULATION).

Large epithelial surface area of the gills act as a respiratory organ, good for
controlling osmoregulation. The gills also aid ion transportation, internal pH
balance and secretions of nitrogenous waste and maintenance. They have a
similar function to the cells in a mammalian stomach that secrete HCL. Fish STC
hormone compared to human stc hormone, although similar in protein molecules,
differ in function. Many studies have focused on the
function and secretion of STC in different species of bony fish, concentrating
on how the hormone transports gill calcium produced by the corpuscles of Stannius.

Current studies suggest certain salmonid STC is more complex than in other
species of fish. Gill calcium transport and passive immunization was tested in
three different species at three different times of the year. Rainbow trout (Oncorhynchus mykiss) was compared to
Chinook salmon (O. tshawytscha) and
parr (young freshwater salmon). After the first experiment that monitored gill
Ca2+ transport in June-July, the trout shown no relationship between
the two parameters in correlation plasma levels of STC, prolactin and growth
hormone. The same outcome occurred in experiment number two and three.

Although, during the first experiment, attempts were made to determine passive
immunization with STC antiserum that could neutralize endogenous STC, this
would significantly raise the rate of GCAT (gill Ca2+ transport).

STC antiserum at a dosage of 10ml/kg elevated transport compared to saline and
NRS (normal rabbit serum) injected trout (see
fig. 2). The assumption that certain species of salmonid have a more
complex form of STC can be neither true or false, during the study the rate of
gill Ca2+ transport (GCAT) over the three species was measured three
times weekly, they appeared to have similar peaks of GCAT that almost mimics
one another (see fig. 3). The study
focused on Rainbow trout compared to the other two species, over the course of
the three experiments they found no significant relationship between the plasma
STC levels and the rate of GCAT in the group of Rainbow trout. The study shown
that the correlation between plasma, prolactin and GCAT may be of significance
and should therefore be investigated in more detail. (molecular and cellular
endocrinology)

Stanniocalcin
in mammals

Because
the corpuscles of Stannius do not exist in mammals, it was long assumed that
STC and its physiological effects on calcium and phosphate homeostasis were
unique to fish (http://www.physiology.org/doi/pdf/10.1152/ajpgi.1998.274.1.G96). STC2
in mammals is at early stages, discussing the overall role and function of STC2
in the body is yet to be concluded, although, recent studies conducted can give
an insight into explaining mammalian STC. in a study conducted by the
Department of Growth and Development, Hiroshima University, scientists tested
STC2 looking for information about the role of STC2 on bones, skeletal tissues
and other tissues. Mouse and rat models were cloned using human STC, this
resulted in high levels of human STC in the liver, heart, adipose tissue,
mammary glands and testis. They concluded that physiological and pathological
processes are regulated by human STC levels and that calcium and phosphate
levels may be the key to these effects, only further evidence of human STC can
help determine exactly what the hormone is responsible for in mammals (stanniocalcin
1 as a pleiotropic factor in mammals).

Claiming to be the first study to examine in detail the
effects of a mammalian form of STC in a mammalian model, Mr G. F. Wagner et al
completed a study based on renal phosphate excretion in the rat, during the
study a group of rats where anesthetized and their urine was collected
throughout the experiment in six intervals, during interval 2, hSTC was
dissolved and given to the rats, blood samples were also taken. At the end of
the experiment the rats were sacrificed and their kidneys were processed. A
second study was then conducted to examine the effects of hSTC on proximal
tubular Na/Pi cotransporter activity, hSTC was given with a
concentration of 5 nmol/kg of body weight or, in control animals, solvent
alone. The rats where killed after 80 minutes and their kidneys were removed. The
results show that hSTC had no effect on renal blood flow, glomerular filtration
rate, urine flow and mean arterial pressure over the course of the three
dosages. Plasma levels of Na+, K+, and Ca2 had
no change during the course of the overall experiment in the hSTC-treated and
control groups of rats (see fig. 1). In conclusion to this study, previous
studies have used fish STC in mammals and have found that it caused
hypercalcemia and hypocalcaemia when given to rats. The kidney in the mammalian
body is one of many tissues that produce the protein in mammals, so it is
unknown yet if STC is targeted there renally. Further studies should address
these questions that need to be answered enabling scientists to understand in
detail human STC.    

Comparison
Case Studies between human STC (hSTC) and fish STC

Human
STC (hSTC) was found to be 247 amino acids long and to share 73% amino acid sequence
similarity with fish STC (http://www.pnas.org/content/93/5/1792.full.pdf).

The relationship between fish STC and newly discovered human STC has prompt
scientist to believe that the two related hormones have clear similarities but
also differences. The topic itself being fairly new means that comparison
studies between them hold little information that can clearly show definite relationships.

What scientists have discovered is that the STC hormone isn’t only produced by
the corpuscles of Stannius in fish, the kidneys in a human body prove to be a
possible source for secreting a similar functioning hormone. Human STC is known
to have been found in different regions of the body, suggesting that it may be an
inhibitor for mineral metabolism. In a recent study, goldfish were injected
with human STC and Salmon STC, another group was injected with saline. The results
shown that gill calcium transport was significantly reduced in comparison to saline-injected
controls (see fig. 5). It is also known
that scientists carry out studies that can compare human STC to other species
of mammal STC, in many cases small rodents are injected to compare renal
functions.

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