Introduction a similar hormone. Human STC shares

Introduction

Homeostasis is the balance of
a consistent internal environment that is regulated by changes internally and
externally. It is controlled by the nervous system and the secretion of
hormones. Internal and external triggers send chemical messages throughout the
body that secrete hormones that are required for important overall regulation. For
example, the hypothalamus works together with other parts of the body to regulate
the body’s temperature, such as sweat glands and blood vessels. Water regulation is controlled by
homeostasis and is regulated by ingesting fluids when thirst is apparent. And
glucose regulation, hormones secreted from the pancreas help control blood sugar
levels, these hormones are called insulin and glucagon that are released when
glucose levels in the body are too high or too low. Stanniocalcin (STC;
previously named hypocalcin or teleocalcin) is a glycoprotein hormone that was
thought to be unique to teleostean and holostean fish (Ishibashi, 2002). Although, it is now known
that humans share a similar hormone. Human STC shares 60% identity and
80% similarity with fish STC (Zhang et
al. 2000). The role of stanniocalcin will be explained in detail including
comparisons of the hormone in bony fish and new studies including STC2 in
mammals and humans.

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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) (Yeung et al.

2011) which is used primarily to protect against hypercalcemia. Initially,
the glands were mistakenly believed to be the piscine equivalents of mammalian
adrenal glands due to their intimate anatomical association with kidneys (Yeung et al 2011). The theory is that
stanniocalcin in bony fish is exclusive as humans and other mammals don’t have
the small endocrine glands. More recent studies comparing fish STC and human
STC suggest that certain human or mammalian STC has similar function to the fish,
and fish STC also has similar functions to mammals. Due to their amino acid
sequence similarity, many studies have been conducted by administering fish STC
or human/mammalian STC and focusing on how the hormone reacts to controls.  

Stanniocalcin
in bony fish

The
main function of STC in fish is to prevent hypercalcemia, and a rise in serum
calcium levels is the primary stimulus for secretion (Madsen et al., 1998) In bony fish, the primary organs for
osmoregulation are the gills or the intestines, their kidneys can’t secrete
hypertonic urine so they use the gills and intestines to help fluid regulation.

Unlike terrestrial mammals, fish face the challenging task of balancing the
dramatic ionic/osmotic gradients between the aquatic environment and their body
fluids (Guh, 2015). The
gills have a large epithelial surface area that act as a respiratory organ, the
same as the kidney works in terrestrial animals. The gills 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 hydrochloric acid. Fish STC hormone compared to human STC hormone,
although similar in protein molecules, differ slightly in function. Fish STC is
known for its regulatory effect on calcium and phosphate transport by the gills,
gut and kidneys (Wagner, 2006). The function and secretion of STC in different species of
bony fish has been researched in depth, concentrating on how the hormone
transports gill calcium around the body and whether or not different species of
fish have different internal strategies of balancing and transporting gill
calcium. Current studies suggest Rainbow trout is more complex than in other
species of fish. Gill calcium transport and passive immunization was tested in
three different species of fish 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, the Rainbow 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 (Madsen et al., 1997).

STC in mammals has recently been discovered and is at early stages of discovery,
discussing the overall role and function of mammalian STC is yet to be
concluded, although, new research can give an insight into explaining mammalian
STC and how it differs compared to fish STC. In a recent study conducted by the
Department of Growth and Development, Hiroshima University, scientists tested mammalian
STC focusing on bones, skeletal tissues and other tissues. Mouse and rat models
were cloned using human STC, the results shown 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 reason why STC is synthesized and secreted. Only
further evidence of human STC tested on other mammals can help determine
exactly what the hormone can manipulate in certain species (Yoshiko, 2004).

 

In another study that claims to be the first to
examine in detail the effects of a mammalian form of STC in a mammalian model,
a study was conducted 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, human STC was
dissolved and administered 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 human STC
on proximal tubular Na/Pi cotransporter activity. Human STC 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 shown that human STC 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.

Previous studies have used
fish STC in certain 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.  

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

The mammalian homolog to fish STC was discovered in
1995 and has resulted in progressively growing interest ever since as to its
possible role in humans (Wagner, 2006). Human
STC was found to be 247 amino acids long and to share 73% amino acid sequence
similarity with fish STC (Olsen et al,.

2006). Scientists have discovered 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, although, gill calcium transport was still noticeable in goldfish
that had been given human STC and salmon STC, proving that the antibodies of
recombinant STC had an effect (see fig. 4).

Scientists will also try and manipulate STC by
administering other hormones that may have an effect on STC secretion. For example,
calcitriol was recently used in a study to show the effects of fish STC (STC1)
and human STC (STC2). The hormone was given to rats over the course of 6 days,
the study focused on the changes of STC levels in the ovaries and kidneys, these
organs were chosen due to have demonstrated high levels of STC1. Changes were measured
by plasma and Ca2+ levels. The results shown that the level of STC1
increased in the kidneys and STC2 decreased (see fig. 6). This supports the theory that STC1 and STC2 are part
of the same stanniocalcin family, and that anti-hypercalcaemic and anti-hypocalcaemic
reactions were restoring normocalcemia. When analysing STC1 and STC2 levels in
the ovaries, both hormone was highly expressed although no changes occurred, this
may suggest an ovary related STC hormone working independently of the calcium
levels.

 

 

 

 

 

 

 

 

 

 

 

Conclusion

When Stanniocalcin was discovered in the human genome, it
was unsure as to whether the hormone displayed the same properties as
stanniocalcin found in fish. It has always been thought that stanniocalcin in
fish is used as an anti-hypercalcaemic glycoprotein (http://www.physiology.org/doi/abs/10.1152/ajpgi.1998.274.1.G96).

Whether it had the same effect on humans was a question many scientists found
themselves asking. When researching the topic, fish STC has clearly been
studied for some time and the information available is widely spread. Although,
human STC is more difficult to uncover, due to the nature of the topic. Now, there
are many different studies surrounding human STC. I found that recent studies
replicated in terms methods and materials used to carry out a scientific study
on human or mammalian STC, although, the results differed across all findings,
and some studies found evidence of new information regarding human STC and fish
STC, such as STC1 and STC2 found in the ovaries of rats over the course of
calcitriol treatment remaining unchanged, suggesting the ovaries are capable of
controlling STC levels independently. As mentioned, research and studies
surrounding human and mammalian STC are of a minority compared to fish STC,
future studies will be the only way scientists can answer questions surrounding
this interesting topic.

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