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Fundamentals

The feeling is unmistakable. A subtle shift in your body’s internal landscape, a change in the way you store energy, a noticeable decline in your vitality. You may have observed that the reflection in the mirror seems different, or that your physical resilience has diminished.

These experiences are valid, and they are rooted in the intricate language of your body’s biochemistry. Your metabolism, the very engine of your cellular life, is governed by a precise communication network. Understanding this network is the first step toward reclaiming your functional vitality. At the heart of this system are two classes of biological communicators ∞ hormones and peptides. They are the architects of your metabolic reality.

Hormones are the body’s far-reaching messengers, produced in specialized glands and sent out through the bloodstream to orchestrate complex, system-wide processes. Think of testosterone, estrogen, and thyroid hormone. They are powerful regulators of growth, mood, and, centrally, your metabolic rate.

They dictate how your body utilizes fuel, whether it stores energy as fat or uses it to build lean tissue. When the production of these key hormones declines, as it does with age, the entire metabolic symphony can fall out of tune. This is often the source of the symptoms you may be experiencing, from persistent fatigue to changes in body composition.

Hormones are powerful, broad-acting messengers that regulate the body’s major metabolic processes.

Peptides, conversely, are highly specific, short-chain amino acid messengers. They function with a much more targeted precision. Where a hormone might send a message to an entire city, a peptide delivers a sealed letter to a single address. Many peptides act as signaling molecules, instructing a gland to produce and release its own native hormones.

They are involved in a vast array of bodily functions, including tissue repair, immune response, and the fine-tuning of metabolic pathways. Their specificity is their greatest asset, allowing for precise interventions that support the body’s innate biological processes. This fundamental difference in scope and action is where the conversation about metabolic optimization begins.

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The Language of Your Cells

Your body’s ability to maintain lean muscle, manage fat stores, and produce consistent energy is a direct reflection of the clarity and strength of its internal signaling. When hormonal signals wane, the instructions for these vital processes become faint.

Traditional hormone replacement therapy (HRT) addresses this by reintroducing the hormones themselves, effectively turning up the volume on those diminished signals. It provides the body with the exact molecule it is missing, such as testosterone or estrogen, to restore systemic function. This approach is direct and can be profoundly effective in correcting a documented deficiency and alleviating its associated symptoms.

Peptide therapies operate on a different principle. They work upstream in the biological hierarchy. Instead of replacing the final hormone, they stimulate the body’s own machinery to produce it. For instance, certain peptides signal the pituitary gland to release growth hormone, a key regulator of metabolism and body composition.

This approach leverages the body’s existing, intelligent feedback loops. It is a way of reminding the system how to function, rather than doing the work for it. The choice between these two paths depends entirely on your individual physiology, your specific metabolic goals, and the underlying nature of your hormonal imbalance.


Intermediate

Advancing our understanding requires moving from the what to the how. The metabolic benefits of any therapeutic intervention are measured by tangible outcomes ∞ improved body composition, enhanced insulin sensitivity, and greater energy production. Both traditional hormonal optimization and peptide therapies can achieve these goals. Their methods for doing so, however, are distinct, targeting different points in the complex web of metabolic regulation. A closer examination of their clinical protocols reveals the unique advantages of each approach.

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Hormonal Optimization and Metabolic Recalibration

Traditional hormone replacement therapy directly addresses the metabolic consequences of hormonal decline. The protocols are designed to restore physiological levels of key hormones, thereby reinstating their powerful influence on the body’s energy economy.

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Testosterone Replacement Therapy and Its Metabolic Impact

For men experiencing andropause, or for women with documented testosterone deficiency, TRT can be transformative. Testosterone has a profound effect on metabolism. It directly stimulates protein synthesis, which is the process of building lean muscle mass. A greater proportion of muscle mass increases the body’s resting metabolic rate, meaning you burn more calories even at rest.

Concurrently, testosterone inhibits the storage of fat, particularly visceral fat, which is the metabolically active fat surrounding the organs that is strongly linked to insulin resistance and other health issues. A standard TRT protocol, often involving weekly injections of Testosterone Cypionate, aims to restore testosterone levels to an optimal range, thereby promoting a leaner, more metabolically active physique.

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Estrogen and Progesterone in Female Metabolic Health

In women, the metabolic shifts of perimenopause and post-menopause are largely driven by the decline in estrogen and progesterone. Estrogen plays a vital role in regulating glucose and lipid metabolism. It helps maintain insulin sensitivity and promotes the healthy distribution of body fat.

As estrogen levels fall, women often experience a shift toward central adiposity and an increased risk of insulin resistance. Hormone therapy for women, which typically involves the administration of estrogen and progesterone, can help mitigate these changes, supporting better blood sugar control and a healthier body composition.

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Peptide Protocols for Targeted Metabolic Enhancement

Peptide therapies offer a more granular approach to metabolic optimization. They do not replace hormones directly. Instead, they use specific signaling molecules to stimulate the body’s own metabolic machinery. This allows for highly targeted interventions that can address specific goals like fat loss, muscle growth, or improved insulin sensitivity.

Peptide therapies utilize specific amino acid chains to signal and enhance the body’s own metabolic functions.

Many of these protocols focus on the Growth Hormone (GH) axis, a central pillar of metabolic regulation. GH plays a critical role in lipolysis (the breakdown of fat) and the synthesis of Insulin-like Growth Factor 1 (IGF-1), which promotes tissue growth and repair. As we age, the pulsatile release of GH from the pituitary gland diminishes. Peptides known as Growth Hormone Releasing Hormone (GHRH) analogs and Growth Hormone Releasing Peptides (GHRPs) can rejuvenate this natural process.

  • Sermorelin ∞ This is a GHRH analog. It directly stimulates the pituitary gland to produce and release its own growth hormone.
  • CJC-1295 and Ipamorelin ∞ This is a very common and synergistic combination. CJC-1295 is another GHRH analog with a longer duration of action, providing a steady stimulus to the pituitary. Ipamorelin is a GHRP that also stimulates GH release through a separate receptor, while having a minimal effect on other hormones like cortisol. Used together, they produce a strong, naturalistic pulse of GH.
  • Tesamorelin ∞ This is a potent GHRH analog that has been specifically studied and approved for the reduction of visceral adipose tissue.
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How Do GLP-1 Agonists Differ from Other Peptides?

A different class of metabolic peptides has gained significant attention ∞ the Glucagon-Like Peptide-1 (GLP-1) receptor agonists. These peptides, including Semaglutide and Tirzepatide, work by mimicking the action of the native hormone GLP-1. This hormone is released by the gut in response to food and has several metabolic effects.

It enhances the release of insulin from the pancreas, suppresses the release of glucagon (a hormone that raises blood sugar), slows gastric emptying to promote feelings of fullness, and acts on the brain to reduce appetite. This multi-pronged mechanism makes GLP-1 agonists exceptionally effective for improving glycemic control and promoting weight loss.

The following table compares the primary mechanisms and metabolic targets of these two distinct therapeutic categories.

Table 1 ∞ Comparison of Metabolic Intervention Strategies
Therapeutic Approach Primary Mechanism of Action Primary Metabolic Target Example Agents
Traditional Hormone Replacement Direct replacement of deficient hormones to restore physiological levels and systemic function. System-wide metabolic regulation, muscle protein synthesis, fat distribution, and insulin sensitivity. Testosterone Cypionate, Estradiol, Progesterone
Growth Hormone Secretagogues Stimulation of the pituitary gland to increase the natural production and release of Growth Hormone. Increased lipolysis (fat breakdown), enhanced muscle growth via IGF-1, and improved body composition. Sermorelin, CJC-1295, Ipamorelin, Tesamorelin
GLP-1 Receptor Agonists Mimicking the action of the native GLP-1 hormone to regulate blood sugar and appetite. Improved glycemic control, reduced appetite, slowed gastric emptying, and significant weight loss. Semaglutide, Tirzepatide


Academic

A sophisticated analysis of metabolic therapies requires an appreciation for the body’s elegant, self-regulating biological axes. The metabolic benefits of any intervention arise from its interaction with these complex systems. The fundamental distinction between traditional hormone replacement and peptide therapies lies in where they intervene in these cascades.

One is a therapy of substitution, the other a therapy of stimulation. This difference has profound physiological implications, particularly when examining the Hypothalamic-Pituitary-Gonadal (HPG) axis and the Growth Hormone (GH) axis from a systems-biology perspective.

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The Principle of End-Organ Substitution versus Upstream Stimulation

Traditional Hormone Replacement Therapy (HRT), such as the administration of exogenous testosterone, operates on the principle of end-organ substitution. It supplies the body with the final, active hormone, bypassing the entire upstream production cascade. When a man receives an injection of Testosterone Cypionate, his serum testosterone levels rise.

This directly stimulates androgen receptors throughout the body, promoting muscle protein synthesis, increasing libido, and exerting other physiological effects. This method is direct, powerful, and effective at correcting a deficiency. It also, however, activates the body’s negative feedback loops.

The hypothalamus and pituitary gland sense the high levels of circulating testosterone and, in response, shut down the production of Gonadotropin-Releasing Hormone (GnRH), Luteinizing Hormone (LH), and Follicle-Stimulating Hormone (FSH). This leads to a downregulation of the body’s endogenous testosterone production and can result in testicular atrophy over time. This is a predictable and manageable consequence, often addressed with adjunctive therapies like Gonadorelin, which mimics GnRH to maintain testicular function.

Peptide therapies, in contrast, are designed to work at the top of the cascade. A peptide like Sermorelin or CJC-1295 is an analog of Growth Hormone-Releasing Hormone (GHRH). It travels to the pituitary gland and binds to GHRH receptors, instructing the somatotroph cells to synthesize and release their own endogenous Growth Hormone.

This process respects the body’s natural pulsatility. GH is naturally released in pulses, primarily during deep sleep, and this pattern is crucial for its optimal physiological effects. Peptide secretagogues work with this rhythm, amplifying the natural pulses rather than creating a constant, unphysiological level of the hormone.

This upstream stimulation preserves the integrity of the feedback loop. The resulting increase in GH and its downstream mediator, IGF-1, still signals back to the hypothalamus to modulate GHRH release, maintaining a state of dynamic equilibrium.

The core distinction lies in replacing a final hormone versus stimulating its natural, pulsatile release from the source.

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Can Peptides Truly Replicate the Full Spectrum of Hormonal Benefits?

This question brings us to the heart of the matter. For metabolic benefits specifically related to the GH axis, peptide therapies can indeed offer similar, and in some ways more physiologically nuanced, outcomes than the administration of exogenous Human Growth Hormone (HGH) itself.

By stimulating the body’s own production, peptides like Tesamorelin can lead to significant reductions in visceral fat and improvements in lipid profiles, mirroring the effects of HGH. The combination of CJC-1295 and Ipamorelin can effectively increase lean body mass and reduce fat mass by elevating GH and IGF-1 levels.

However, peptides cannot fully replicate the metabolic benefits of sex hormone replacement. There is no peptide that can substitute for the broad, systemic effects of testosterone or estrogen. Peptides can support the HPG axis; for example, Gonadorelin can stimulate LH and FSH production. But they cannot create testosterone or estrogen.

Therefore, in cases of primary hypogonadism or menopause, where the gonads themselves have lost their ability to produce sufficient hormones, direct replacement is the only viable method to restore those specific hormonal functions. A peptide can knock on the door of the factory, but it cannot build a new factory.

In these scenarios, peptide therapies can be a powerful adjunct to HRT, but not a replacement. For example, a man on TRT might also use a GH-stimulating peptide to further enhance fat loss and recovery, creating a synergistic effect.

A skeletonized leaf on a green surface visually portrays the delicate endocrine system and effects of hormonal imbalance. This emphasizes the precision of Hormone Replacement Therapy HRT, including Testosterone Replacement Therapy TRT and peptide protocols, crucial for cellular repair, restoring homeostasis, and achieving hormone optimization for reclaimed vitality

A Deeper Look at Cellular Mechanisms

The table below provides a granular comparison of the physiological cascade initiated by direct testosterone administration versus a GHRH/GHRP peptide combination.

Table 2 ∞ Physiological Cascade Comparison
Parameter Testosterone Replacement Therapy (TRT) Peptide Therapy (e.g. CJC-1295/Ipamorelin)
Initial Signal Exogenous testosterone introduced into circulation. Exogenous GHRH/GHRP peptides introduced into circulation.
Primary Target Organ Androgen receptors on cells throughout the body (muscle, bone, brain, fat). GHRH and Ghrelin receptors on somatotroph cells in the anterior pituitary gland.
Effect on Pituitary Inhibition of LH and FSH release via negative feedback. Stimulation of endogenous Growth Hormone (GH) synthesis and release.
Hormonal Result Supraphysiological, stable levels of serum testosterone. Endogenous production is suppressed. Pulsatile release of endogenous GH, leading to increased serum GH and subsequently IGF-1.
Metabolic Outcome Increased muscle protein synthesis, decreased adiposity, improved insulin sensitivity. Increased lipolysis, increased protein synthesis (via IGF-1), improved body composition.
Feedback Loop Integrity The natural HPG axis feedback loop is overridden and suppressed. The natural GH axis feedback loop is preserved and modulated.

This analysis reveals that while both pathways can lead to favorable metabolic outcomes like increased muscle and decreased fat, their interaction with the body’s endocrine architecture is fundamentally different. The choice of therapy is therefore a strategic decision based on the specific physiological state and therapeutic goals of the individual.

For an individual with a healthy, responsive pituitary gland who wishes to optimize body composition, peptide therapy offers a method of enhancing natural function. For an individual with primary testicular failure, direct testosterone replacement is necessary to correct the core deficiency.

  1. System Integrity ∞ Peptide therapies for GH stimulation work by enhancing the body’s existing systems, preserving the natural pulsatile release and feedback mechanisms that are critical for long-term health and optimal function.
  2. Specificity of Action ∞ While HRT provides a broad, systemic effect by replacing a key hormone, peptides allow for a more targeted approach. Peptides like GLP-1 agonists focus specifically on glucose metabolism and appetite, while others focus on stimulating the GH axis.
  3. Complementary Roles ∞ The most sophisticated protocols often involve a synthesis of both approaches. An individual may use HRT to establish a healthy hormonal baseline and then layer on specific peptide therapies to fine-tune metabolic parameters or accelerate tissue repair, achieving a level of optimization that neither therapy could provide alone.

A delicate, skeletal botanical structure symbolizes the intricate nature of the human endocrine system. It visually represents the impact of hormonal imbalance in conditions like perimenopause and hypogonadism, underscoring the necessity for precise hormone optimization through Bioidentical Hormone Replacement Therapy BHRT and advanced peptide protocols to restore cellular regeneration and metabolic health

References

  • Velloso, C. P. “Regulation of muscle mass by growth hormone and IGF-I.” British Journal of Pharmacology, vol. 154, no. 3, 2008, pp. 557-568.
  • Sigalos, J. T. and A. W. Pastuszak. “The Safety and Efficacy of Growth Hormone Secretagogues.” Sexual Medicine Reviews, vol. 6, no. 1, 2018, pp. 45-53.
  • Fields, D. A. et al. “Tesamorelin, a growth hormone-releasing hormone analog, improves lipids and reduces visceral adiposity in human immunodeficiency virus-infected patients with abdominal fat accumulation.” The Journal of Clinical Endocrinology & Metabolism, vol. 93, no. 9, 2008, pp. 3420-3427.
  • Drucker, D. J. and M. A. Nauck. “The incretin system ∞ glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes.” The Lancet, vol. 368, no. 9548, 2006, pp. 1696-1705.
  • Khorram, O. et al. “Effects of a 12-week administration of a growth hormone-releasing hormone (GHRH) analog on pituitary and gonadal function in healthy men.” The Journal of Clinical Endocrinology & Metabolism, vol. 82, no. 2, 1997, pp. 528-533.
  • Sattler, F. R. et al. “Testosterone and growth hormone improve body composition and muscle performance in older men.” Journal of Clinical Endocrinology & Metabolism, vol. 94, no. 6, 2009, pp. 1991-2001.
  • Frühbeck, G. et al. “The adipocyte ∞ a model for integration of endocrine and metabolic signaling in energy metabolism regulation.” American Journal of Physiology-Endocrinology and Metabolism, vol. 280, no. 6, 2001, pp. E827-E847.
  • Clemmons, D. R. “The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity.” Journal of Clinical Investigation, vol. 113, no. 1, 2004, pp. 25-27.
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Reflection

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Charting Your Own Biological Course

The information presented here is a map. It details the pathways, the mechanisms, and the potential destinations available through modern metabolic medicine. Yet, a map is not the territory. Your body is the territory, a unique and dynamic landscape shaped by your genetics, your history, and your daily choices.

The purpose of this knowledge is not to provide a simple answer, but to equip you with a better set of questions. As you stand before your own health journey, consider where your symptoms point on this map. Reflect on whether your goals align with a therapy of substitution or one of stimulation.

The most profound insight is recognizing that your lived experience and your biological data are two parts of the same story. Understanding how to read that story is the beginning of learning how to write the next chapter yourself.

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Glossary

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body composition

Meaning ∞ Body composition refers to the proportional distribution of the primary constituents that make up the human body, specifically distinguishing between fat mass and fat-free mass, which includes muscle, bone, and water.
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traditional hormone replacement therapy

Meaning ∞ Traditional Hormone Replacement Therapy involves the systemic administration of exogenous estrogen, often combined with progestogen, to alleviate symptoms associated with hormonal decline, primarily during the menopausal transition.
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peptide therapies

Meaning ∞ Peptide therapies involve the administration of specific amino acid chains, known as peptides, to modulate physiological functions and address various health conditions.
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pituitary gland

Meaning ∞ The Pituitary Gland is a small, pea-sized endocrine gland situated at the base of the brain, precisely within a bony structure called the sella turcica.
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improved body composition

Improved vascular reactivity from hormonal optimization is shown by lower inflammation markers and enhanced arterial blood flow.
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insulin sensitivity

Meaning ∞ Insulin sensitivity refers to the degree to which cells in the body, particularly muscle, fat, and liver cells, respond effectively to insulin's signal to take up glucose from the bloodstream.
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traditional hormone replacement

Meaning ∞ Traditional Hormone Replacement administers exogenous hormones to address endocrine deficiencies.
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protein synthesis

Meaning ∞ Protein synthesis is the fundamental biological process by which living cells create new proteins, essential macromolecules for virtually all cellular functions.
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trt

Meaning ∞ Testosterone Replacement Therapy, or TRT, is a clinical intervention designed to restore physiological testosterone levels in individuals diagnosed with hypogonadism.
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estrogen and progesterone

Meaning ∞ Estrogen and progesterone are vital steroid hormones, primarily synthesized by the ovaries in females, with contributions from adrenal glands, fat tissue, and the placenta.
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pulsatile release

Meaning ∞ Pulsatile release refers to the episodic, intermittent secretion of biological substances, typically hormones, in discrete bursts rather than a continuous, steady flow.
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growth hormone

Meaning ∞ Growth hormone, or somatotropin, is a peptide hormone synthesized by the anterior pituitary gland, essential for stimulating cellular reproduction, regeneration, and somatic growth.
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ghrh analog

Meaning ∞ A GHRH analog is a synthetic compound mimicking natural Growth Hormone-Releasing Hormone (GHRH).
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ipamorelin

Meaning ∞ Ipamorelin is a synthetic peptide, a growth hormone-releasing peptide (GHRP), functioning as a selective agonist of the ghrelin/growth hormone secretagogue receptor (GHS-R).
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cjc-1295

Meaning ∞ CJC-1295 is a synthetic peptide, a long-acting analog of growth hormone-releasing hormone (GHRH).
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tesamorelin

Meaning ∞ Tesamorelin is a synthetic peptide analog of Growth Hormone-Releasing Hormone (GHRH).
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semaglutide

Meaning ∞ Semaglutide is a synthetic analog of human glucagon-like peptide-1 (GLP-1), functioning as a GLP-1 receptor agonist.
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hormone replacement

Meaning ∞ Hormone Replacement involves the exogenous administration of specific hormones to individuals whose endogenous production is insufficient or absent, aiming to restore physiological levels and alleviate symptoms associated with hormonal deficiency.
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metabolic benefits

Meaning ∞ Metabolic benefits denote positive physiological adaptations optimizing the body's energy production, utilization, and storage.
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hormone replacement therapy

Meaning ∞ Hormone Replacement Therapy, often referred to as HRT, involves the administration of exogenous hormones to supplement or replace endogenous hormones that are deficient or absent in the body.
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muscle protein synthesis

Meaning ∞ Muscle protein synthesis refers to the fundamental physiological process where the body generates new muscle proteins from available amino acids.
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growth hormone-releasing hormone

Meaning ∞ Growth Hormone-Releasing Hormone, commonly known as GHRH, is a specific neurohormone produced in the hypothalamus.
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feedback loop

Meaning ∞ A feedback loop describes a fundamental biological regulatory mechanism where the output of a system influences its own input, thereby modulating its activity to maintain physiological balance.
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hpg axis

Meaning ∞ The HPG Axis, or Hypothalamic-Pituitary-Gonadal Axis, is a fundamental neuroendocrine pathway regulating human reproductive and sexual functions.
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peptide therapy

Meaning ∞ Peptide therapy involves the therapeutic administration of specific amino acid chains, known as peptides, to modulate various physiological functions.