Synonym |
(D-His2)-LHRH |
Species |
Human |
Protein Accession |
P01148 |
Purity |
Greater than 95% |
Endotoxin Level |
Less than 1 EU/ug |
Biological Activity |
The ED50 as determined by the dose-dependent stimulation of the release of luteinizing hormone
from cultured rat pituitary cells is less than 1.0 ng/ml, corresponding to a specific activity
of > 1.0 x 10^6 IU/mg. |
Expression System |
E. coli |
Fusion Tag |
No tag |
Predicted Molecular Mass |
1181 Da |
Formulation |
Lyophilized from a sterile filtered solution of 10 mM HCl |
Reconstitution |
It is recommended to reconstitute the lyophilized (D-His2)-LHRH in sterile 18MΩ-cm H2O not less
than 100 µg/ml, which can then be further diluted to other aqueous solutions. |
Storage & Stability |
Lyophilized (D-His2)-LHRH although stable at room temperature for 3 weeks, should be stored
desiccated below -18°C. Upon reconstitution (D-His2)-LHRH should be stored at 4°C between 2-7
days and for future use below -18°C. |
FAQ
What is (D-His2)-LHRH and how does it function in the body?
(D-His2)-LHRH is a synthetic analogue
of the naturally occurring luteinizing hormone-releasing hormone (LHRH or GnRH), which plays a crucial
role in regulating the reproductive system. This peptide is a modified version of the hormone with a
specific alteration at the second position—where histidine is replaced by its isomer, D-His, to increase
its stability and effectiveness. (D-His2)-LHRH is primarily utilized in research settings to better
understand how hormonal regulation influences reproductive physiology and related processes.
LHRH
is released by the hypothalamus and acts upon the anterior pituitary gland to stimulate the secretion of
luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones are vital for normal
functioning of the ovaries in females and the testes in males. In females, this cascade promotes the
maturation of follicles in the ovaries and triggers ovulation. In males, LH stimulates testosterone
production while FSH is key for sperm production. Altering the LHRH molecule, as in the case of
(D-His2)-LHRH, can affect the responsive hormonal pattern and provides a tool for examining pathway
effectiveness under various conditions.
The modified analogue (D-His2)-LHRH can be used to better
understand and potentially influence fertility treatments. Researchers can observe how specific changes
in LHRH structures alter its interaction with receptors, thus impacting subsequent hormone cascade
efficacy. This analogue can also be pivotal in studies aimed at deciphering hormonal dysfunctions or
developing methods to manipulate hormone production for therapeutic purposes. For instance, this
modified peptide could be explored as a means to proactively control or influence fertility, or even as
part of hormone-related cancer research where the suppression of specific hormone activities is crucial.
Above all, (D-His2)-LHRH serves as a powerful research tool, aiding scientists in decoding the
intricacies of hormonal interactions pertinent to reproduction and broader endocrine health.
How
might researchers utilize (D-His2)-LHRH in the context of medical research and treatment
development?
Researchers employ (D-His2)-LHRH in various contexts, notably within reproductive
medicine and hormone-dependant disease treatments. This analogue serves as a pivotal tool for expanding
our understanding of hormonal regulation and offers potential therapeutic avenues. One of the primary
areas of employment for (D-His2)-LHRH is in fertility research. By applying this synthetic hormone,
scientists can explore distinct physiological responses, testing how it alters the secretion of LH and
FSH. This examination can provide insights into ovulatory cycles, spermatogenesis, and more nuanced
aspects of reproductive endocrinology, offering enhanced understanding of infertility
issues.
Furthermore, (D-His2)-LHRH can be instrumental in developing treatments for
hormone-responsive cancers, such as those affecting the prostate or breast. These malignancies often
rely on hormonal stimuli for growth and proliferation. Through the adjustment or attenuation of hormone
signals, such as those initiated by LHRH, researchers can develop strategies that diminish hormone
production or block receptor activation, thereby stunting cancer growth. As a result, (D-His2)-LHRH may
pave the way for novel therapeutics that effectively mediate these pathways to provide improved outcomes
for patients.
Beyond reproductive health and oncology, (D-His2)-LHRH might offer solutions for
managing hormone-related conditions like polycystic ovary syndrome (PCOS) or endometriosis, where
hormone regulation plays a critical role in disease management. By manipulating hormonal output,
(D-His2)-LHRH presents the possibility of alleviating symptoms or reducing disease severity in such
cases.
Furthermore, as scientists continue to expand the application of peptide-based drugs,
(D-His2)-LHRH remains at the forefront of innovative peptide therapy development. Its stability and
receptor affinity offer significant advantages in preclinical studies aimed at developing targeted
therapies, exemplifying its invaluable role in translational research. The research on (D-His2)-LHRH
thus extends beyond theoretical exploration, offering practical applicability in therapeutic innovation,
which continues to develop as technologies and methodologies improve.
What are the safety
considerations and potential side effects associated with the use of (D-His2)-LHRH in research
settings?
When using (D-His2)-LHRH in research settings, it is important to consider both the
potential biological effects and hazards associated with handling synthetic peptides. As a chemical
entity, it must be carefully managed to avoid exposure risks, which are typically mitigated through
standard laboratory safety protocols. Protective equipment, such as gloves and safety goggles, should be
worn to prevent direct skin contact or accidental ingestion or inhalation, and experiments should be
conducted within controlled environments, like laminar flow hoods, to prevent cross-contamination or
exposure.
In terms of biological safety, the administration of (D-His2)-LHRH to biological models
can elicit a variety of physiological responses, depending on the dosage and method of administration.
By imitating natural LHRH, this analogue could potentially alter hormonal balances, leading to side
effects similar to those observed with natural hormone therapies. These could include changes in
reproductive function, such as altered menstrual cycles or impacts on testosterone production.
Experiments need to be designed carefully to monitor these impacts, particularly when working with
animal models.
When extrapolating data from animal studies to human applications, researchers
must proceed cautiously. Side effects observed in animal models do not always accurately predict human
responses due to biological and metabolic differences. Nonetheless, these observations provide a
critical foundation for assessing the potential impacts on hormone levels, reproductive cycles, or other
physiological parameters.
It's also crucial to consider potential long-term effects and the
duration of the hormone alteration. Chronic exposure or improper dosing could lead to sustained hormonal
imbalance or negative feedback effects on the hypothalamic-pituitary-gonadal axis, which must be managed
through tailored experimental designs.
Moreover, since (D-His2)-LHRH may interact differently
with various receptors, understanding receptor-specific activity is key. Detailed receptor binding
studies should be carried out to elucidate these interactions, ensuring that the analogue's behavior
within biological systems is thoroughly understood. Such investigations aid in anticipating and
mitigating unintended effects, reinforcing the importance of established preclinical safety assessments
and appropriate dosing regimens.
How does (D-His2)-LHRH differ from other LHRH analogues in terms
of stability and efficacy?
(D-His2)-LHRH is distinguished from other LHRH analogues mainly by its
structural modification at the second position, where the natural amino acid histidine is replaced with
D-His, an isomer of histidine. This specific alteration enhances both the stability and efficacy of the
peptide compared to its natural counterpart. The inclusion of D-His impedes enzymatic degradation,
thereby extending the analogue's half-life in biological systems. Increased stability allows for a
prolonged therapeutic window and reduces the frequency of administration, which can be particularly
beneficial in long-term treatment or research contexts.
The efficacy of (D-His2)-LHRH is linked
to its ability to maintain biological activity despite its structural modifications. It retains the
capacity to bind effectively to LHRH receptors, ensuring that the essential signaling cascade is
initiated efficiently. The selective receptor affinity of (D-His2)-LHRH contributes to its role as an
effective tool in research settings, enabling precise modulation of reproductive hormones like LH and
FSH. This precision is fundamental when investigating cellular responses, testing hypotheses within
endocrine research, or exploring novel therapeutic approaches.
Additionally, the unique stability
attributes of (D-His2)-LHRH facilitate its use under varying experimental conditions, including those
that mimic human physiological environments or altered states in disease models. Its ability to sustain
activity over extended periods presents researchers with enhanced flexibility in experimental design and
specificity in observing time-dependent hormonal effects.
In contrast, other LHRH analogues might
not offer the same level of receptor specificity or stability, which can limit their application or
require more frequent dosing. The development of such analogues is multifaceted, focusing on achieving
an optimal balance between stability, receptor binding efficiency, and biological impact. The choice
among available analogues, therefore, hinges on the specific requirements of a study or treatment, where
(D-His2)-LHRH might be preferred for leveraging its distinct attributes that align with desired research
or therapeutic outcomes.
What are the potential implications of using (D-His2)-LHRH in the
treatment of endocrine disorders?
The application of (D-His2)-LHRH in treating endocrine
disorders holds considerable promise due to its ability to modulate hormonal pathways precisely.
Endocrine disorders, characterized by dysregulation in hormone production or signaling, often require
targeted therapeutic strategies to restore balance. By virtue of its modified peptide structure,
(D-His2)-LHRH functions with increased stability and receptor affinity, offering nuanced control over
hormone-dependent pathways. This makes it a valuable candidate for addressing disorders such as
hypogonadism, polycystic ovary syndrome (PCOS), and hormone-sensitive cancers.
In the treatment
of hypogonadism, where patients exhibit insufficient hormone production leading to underdeveloped
secondary sexual characteristics or reproductive issues, (D-His2)-LHRH can be utilized to stimulate the
pituitary release of gonadotropins (LH and FSH). By doing so, it can promote gonadal function, thereby
increasing the production of sex steroids and supporting normal reproductive physiology. This treatment
approach could significantly improve quality of life and assist in resolving underlying symptoms
associated with hormonal deficiency.
For conditions like PCOS, where hormonal imbalance leads to
irregular ovulation and other physical manifestations, (D-His2)-LHRH might offer therapeutic advantages
by effectively controlling hormonal outputs that contribute to ovulatory dysfunction. By manipulating
the hypothalamic-pituitary-ovarian axis, it might be possible to mitigate the reproductive challenges
posed by this syndrome.
Moreover, in the realm of cancer therapy, particularly for
hormone-sensitive types like certain prostate and breast cancers, (D-His2)-LHRH might be used to
suppress the hormonal signals that fuel cancer cell proliferation. By acting on the LHRH receptors to
downregulate gonadotropin release, it can reduce the levels of sex steroids that are often necessary for
tumor growth. This mechanism of action presents a non-surgical option drawn from hormonal manipulation,
which is less invasive and can be tailored in dosing.
The exploration of (D-His2)-LHRH's
potential extends beyond reproductive health into broader endocrine applications, where precision in
hormone regulation is critical. As researchers continue to unravel the diverse roles of peptides in
clinical settings, (D-His2)-LHRH represents a promising frontier in the ongoing effort to devise
effective, targeted therapies for complex endocrine disorders.