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Testosterone Replacement, Low T, HCG, & Beyond
When Testosterone Is Not Enough
Kisspeptin suppression under TRT: Can it affect mood and libido?
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<blockquote data-quote="madman" data-source="post: 245178" data-attributes="member: 13851"><p>Bet those run-of-the-mill clinics will go ape shit pushing injectable KP-10 as the next best thing!</p><p></p><p>Everyone needs to keep this in mind!</p><p></p><p></p><p><em><strong>*KP-10, KP-54, and kisspeptin receptor agonists such as TAK-683 [11] and MVT-602 (formerly known as TAK448) [12] are the kisspeptin peptides that have been studied in humans to date. <u>KP-10 is potent against KISS1R in vitro but is not believed to cross the blood-brain barrier and has a shorter half-life than KP-54 (t1/2 3 vs. 28 min) due to significant enzymatic degradation, making it less suitable for bolus administration</u> [2]. <u>Native KP-54 has a longer half-life and induces greater LH rises in vivo after bolus administration</u> but is more expensive to manufacture than KP-10 due to its longer peptide length [13].</strong> <strong><u>KISS1R-analogs, such as TAK-683 and MVT-602, which have been recently developed by modification of KP-10, possess increased stability and potency, hence enabling more cost-effective peptide manufacture</u> [11,12].</strong></em></p><p><em><strong></strong></em></p><p><em><strong></strong></em></p><p><em><strong>*different <u>kisspeptin peptide forms (KP-54, KP-10, KP-analogue), durations, frequencies (bolus or continuous infusion), and administration routes (central, subcutaneous, intranasal, or intravenous)</u> </strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/forum/threads/novel-therapeutic-avenues-for-kisspeptin.26563/[/URL]</p><p></p><p></p><p><strong>Background</strong></p><p></p><p><em>The kisspeptins are a family of peptides encoded by the KISS1 gene in humans (KISS1 in non-human primates and Kiss1 in other mammals) [1].<strong> The prepropeptide consists of 145 amino acids that are subsequently proteolyzed into shorter peptides of lengths denoted by their suffixes, such as <u>kisspeptin-54 (KP-54), -14, -13, and -10 (KP-10)</u> [2]. </strong>All forms share a common C-terminal decapeptide sequence, equivalent to KP-10, which is important for their binding to the G-protein-coupled kisspeptin receptor, KISS1R (formerly known as the orphan receptor GRP54) [2].<strong> Kisspeptin primarily stimulates the hypothalamus to regulate the hypothalamic-pituitary-gonadal axis [3]. Indeed, the decreased KISS1R signaling in humans results in absent puberty and hypogonadotropic hypogonadism [4,5], whereas increased KISS1R signaling results in precocious puberty [6]</strong></em></p><p><em><strong></strong></em></p><p><em><strong>Outside the human hypothalamus [7], kisspeptin and its receptor are expressed in the brain in key limbic and paralimbic regions [7], and in peripheral tissues such as the gonads, placenta, liver, adipose tissue, and bone [7]. Consequently, beyond its central role in stimulating hypothalamic gonadotrophin-releasing hormone (GnRH) secretion, kisspeptin has been studied in sexual and emotional brain processing [7], bone turnover [8], metabolism [9], and as a biomarker of pregnancy complications [10]. Herein, we summarise data on the pharmacological use of kisspeptin in reproductive disorders and fertility treatment, as well as its putative utility in hypoactive sexual desire disorder (HSDD), osteoporosis, and non-alcoholic fatty liver disease, now known as metabolic dysfunction-associated fatty liver disease (MAFLD) (Figure 1).</strong></em></p><p></p><p></p><p></p><p></p><p><strong>Kisspeptin trials in healthy men and women</strong></p><p></p><p><em>KP-10, KP-54, and kisspeptin receptor agonists such as TAK-683 [11] and MVT-602 (formerly known as TAK448) [12] are the kisspeptin peptides that have been studied in humans to date.<strong> <u>KP-10 is potent against KISS1R in vitro but is not believed to cross the blood-brain barrier and has a shorter half-life than KP-54 (t1/2 3 vs. 28 min)</u> due to significant enzymatic degradation, making it less suitable for bolus administration [2]. <u>Native KP-54 has a longer half-life and induces greater LH rises in vivo after bolus administration</u> but is more expensive to manufacture than KP-10 due to its longer peptide length [13].</strong> <strong><u>KISS1R-analogs, such as TAK-683 and MVT-602, which have been recently developed by modification of KP-10, possess increased stability and potency, hence enabling more cost-effective peptide manufacture</u> [11,12].</strong></em></p><p><em><strong></strong></em></p><p><em><strong>Exogenous kisspeptin has been reported to potently stimulate GnRH and in turn luteinizing hormone (LH), in healthy men and women, and in patients with the reproductive disease, using different <u>kisspeptin peptide forms (KP-54, KP-10, KP-analogue), durations, frequencies (bolus or continuous infusion) and administration routes (central, subcutaneous, intranasal or intravenous)</u> [2,14-19]. </strong>Subcutaneous KP-54 stimulated gonadotrophin secretion in healthy females throughout all phases of their menstrual cycle [18,20,21], but with the greatest LH rises during the preovulatory phase [18,22e24]. Intravenous KP-10 was the least effective during the follicular phase of the menstrual cycle and evoked no gonadotrophin response when administered subcutaneously [25,26].</em></p><p><em></em></p><p><em><strong>In healthy men, both an intravenous bolus and a continuous infusion of <u>KP-10 produced significant LH responses with the latter maintaining LH secretion for at least 22.5 h</u> [17,25]. Acute and chronic administration of intravenous KP-10-induced LH increases in obese hypogonadal diabetic men [27] and healthy older men [28], thereby highlighting promising therapeutic avenues for the use of kisspeptin in male functional hypogonadism related to diabetes, obesity, or age.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>Recently, <u>kisspeptin receptor agonists, including MVT-602 and TAK-683</u>, were shown to potently increase LH secretion in men and women [12,29-31].</strong> MVT-602 administered during the follicular phase of the menstrual cycle of healthy women triggered a similar LH amplitude to KP-54 yet produced a more sustained LH rise, with a correspondingly increased area under the curve of LH rise [12]. However, pharmacokinetic properties were similar between MVT-602 and KP-54, suggesting that the longer duration of effect was centered on differential activation of the kisspeptin receptor [12]. When studied in vitro on mouse GnRH neurons, MVT-602 was more potent and induced a more sustained duration of GnRH-neuronal firing than KP-54 (115 vs. 55 min) [12]. <strong>Importantly, kisspeptins have been administered to a few hundred patients by different research groups and to different populations but have not been associated with any adverse effects [11,15-17,32-34]. Indeed, kisspeptin levels increase dramatically during pregnancy from non-pregnant levels (8 pmol/L) to 1230 pmol/L during the first trimester and 9590 pmol/L during the third trimester [35e37], consistent with the reported wide therapeutic safety window [10].</strong></em></p></blockquote><p></p>
[QUOTE="madman, post: 245178, member: 13851"] Bet those run-of-the-mill clinics will go ape shit pushing injectable KP-10 as the next best thing! Everyone needs to keep this in mind! [I][B]*KP-10, KP-54, and kisspeptin receptor agonists such as TAK-683 [11] and MVT-602 (formerly known as TAK448) [12] are the kisspeptin peptides that have been studied in humans to date. [U]KP-10 is potent against KISS1R in vitro but is not believed to cross the blood-brain barrier and has a shorter half-life than KP-54 (t1/2 3 vs. 28 min) due to significant enzymatic degradation, making it less suitable for bolus administration[/U] [2]. [U]Native KP-54 has a longer half-life and induces greater LH rises in vivo after bolus administration[/U] but is more expensive to manufacture than KP-10 due to its longer peptide length [13].[/B] [B][U]KISS1R-analogs, such as TAK-683 and MVT-602, which have been recently developed by modification of KP-10, possess increased stability and potency, hence enabling more cost-effective peptide manufacture[/U] [11,12]. *different [U]kisspeptin peptide forms (KP-54, KP-10, KP-analogue), durations, frequencies (bolus or continuous infusion), and administration routes (central, subcutaneous, intranasal, or intravenous)[/U] [/B][/I] [URL unfurl="true"]https://www.excelmale.com/forum/threads/novel-therapeutic-avenues-for-kisspeptin.26563/[/URL] [B]Background[/B] [I]The kisspeptins are a family of peptides encoded by the KISS1 gene in humans (KISS1 in non-human primates and Kiss1 in other mammals) [1].[B] The prepropeptide consists of 145 amino acids that are subsequently proteolyzed into shorter peptides of lengths denoted by their suffixes, such as [U]kisspeptin-54 (KP-54), -14, -13, and -10 (KP-10)[/U] [2]. [/B]All forms share a common C-terminal decapeptide sequence, equivalent to KP-10, which is important for their binding to the G-protein-coupled kisspeptin receptor, KISS1R (formerly known as the orphan receptor GRP54) [2].[B] Kisspeptin primarily stimulates the hypothalamus to regulate the hypothalamic-pituitary-gonadal axis [3]. Indeed, the decreased KISS1R signaling in humans results in absent puberty and hypogonadotropic hypogonadism [4,5], whereas increased KISS1R signaling results in precocious puberty [6] Outside the human hypothalamus [7], kisspeptin and its receptor are expressed in the brain in key limbic and paralimbic regions [7], and in peripheral tissues such as the gonads, placenta, liver, adipose tissue, and bone [7]. Consequently, beyond its central role in stimulating hypothalamic gonadotrophin-releasing hormone (GnRH) secretion, kisspeptin has been studied in sexual and emotional brain processing [7], bone turnover [8], metabolism [9], and as a biomarker of pregnancy complications [10]. Herein, we summarise data on the pharmacological use of kisspeptin in reproductive disorders and fertility treatment, as well as its putative utility in hypoactive sexual desire disorder (HSDD), osteoporosis, and non-alcoholic fatty liver disease, now known as metabolic dysfunction-associated fatty liver disease (MAFLD) (Figure 1).[/B][/I] [B]Kisspeptin trials in healthy men and women[/B] [I]KP-10, KP-54, and kisspeptin receptor agonists such as TAK-683 [11] and MVT-602 (formerly known as TAK448) [12] are the kisspeptin peptides that have been studied in humans to date.[B] [U]KP-10 is potent against KISS1R in vitro but is not believed to cross the blood-brain barrier and has a shorter half-life than KP-54 (t1/2 3 vs. 28 min)[/U] due to significant enzymatic degradation, making it less suitable for bolus administration [2]. [U]Native KP-54 has a longer half-life and induces greater LH rises in vivo after bolus administration[/U] but is more expensive to manufacture than KP-10 due to its longer peptide length [13].[/B] [B][U]KISS1R-analogs, such as TAK-683 and MVT-602, which have been recently developed by modification of KP-10, possess increased stability and potency, hence enabling more cost-effective peptide manufacture[/U] [11,12]. Exogenous kisspeptin has been reported to potently stimulate GnRH and in turn luteinizing hormone (LH), in healthy men and women, and in patients with the reproductive disease, using different [U]kisspeptin peptide forms (KP-54, KP-10, KP-analogue), durations, frequencies (bolus or continuous infusion) and administration routes (central, subcutaneous, intranasal or intravenous)[/U] [2,14-19]. [/B]Subcutaneous KP-54 stimulated gonadotrophin secretion in healthy females throughout all phases of their menstrual cycle [18,20,21], but with the greatest LH rises during the preovulatory phase [18,22e24]. Intravenous KP-10 was the least effective during the follicular phase of the menstrual cycle and evoked no gonadotrophin response when administered subcutaneously [25,26]. [B]In healthy men, both an intravenous bolus and a continuous infusion of [U]KP-10 produced significant LH responses with the latter maintaining LH secretion for at least 22.5 h[/U] [17,25]. Acute and chronic administration of intravenous KP-10-induced LH increases in obese hypogonadal diabetic men [27] and healthy older men [28], thereby highlighting promising therapeutic avenues for the use of kisspeptin in male functional hypogonadism related to diabetes, obesity, or age. Recently, [U]kisspeptin receptor agonists, including MVT-602 and TAK-683[/U], were shown to potently increase LH secretion in men and women [12,29-31].[/B] MVT-602 administered during the follicular phase of the menstrual cycle of healthy women triggered a similar LH amplitude to KP-54 yet produced a more sustained LH rise, with a correspondingly increased area under the curve of LH rise [12]. However, pharmacokinetic properties were similar between MVT-602 and KP-54, suggesting that the longer duration of effect was centered on differential activation of the kisspeptin receptor [12]. When studied in vitro on mouse GnRH neurons, MVT-602 was more potent and induced a more sustained duration of GnRH-neuronal firing than KP-54 (115 vs. 55 min) [12]. [B]Importantly, kisspeptins have been administered to a few hundred patients by different research groups and to different populations but have not been associated with any adverse effects [11,15-17,32-34]. Indeed, kisspeptin levels increase dramatically during pregnancy from non-pregnant levels (8 pmol/L) to 1230 pmol/L during the first trimester and 9590 pmol/L during the third trimester [35e37], consistent with the reported wide therapeutic safety window [10].[/B][/I] [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
When Testosterone Is Not Enough
Kisspeptin suppression under TRT: Can it affect mood and libido?
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