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Jan Fahrenkrug - One of the best experts on this subject based on the ideXlab platform.

  • Expression and characterization of preproVIP derived Peptides in the human male urogenital tract.
    Neuropeptides, 1995
    Co-Authors: B. Ottesen, H.e Bredkjaer, E Ekblad, S Krause, J Miskowiak, Jan Fahrenkrug
    Abstract:

    Abstract Expression of the gene sequence encoding vasoactive intestinal polyPeptide (VIP) leads to the synthesis of a 170 amino acid precursor molecule which can be processed to five fragments: preproVIP 22–79, Peptide Histidine Methionine (PHM), or Peptide Histidine valine (PHV), preproVIP 111–122, VIP and preproVIP 156–170. Using region specific radioimmunoassays and antisera against the functional domains of the VIP precursor in combination with immunocytochemistry and chromatography, the localization, distribution and identify of the preproVIP derived Peptides within the human male urogenital tract were investigated. Postmortem as well as fresh tissue specimens were used. All the preproVIP derived Peptides were expressed and could be demonstrated in nerve fibres throughout the urogenital tract in close relation to the epithelial lining and in vascular as well as non-vascular smooth muscle. The VIP-related Peptide containing fibres were most abundant in the prostate parenchyma and the seminal vesicle. Using double immunostaining, co-localization of the various preproVIP derived Peptides could be evidenced. The fact that all preproVIP derived Peptides are present in the urogenital tract, should be taken into consideration when the regulatory aspects of neuroPeptides in physiological and pathophysiological functions are discussed.

  • Location of PHM/VIP mRNA in human gastrointestinal tract detected by in situ hybridization
    Cell and Tissue Research, 1994
    Co-Authors: Helle E. Bredkjær, Birgitte S. Wulff, Piers C. Emson, Jan Fahrenkrug
    Abstract:

    The expression of the gene for vasoactive intestinal polyPeptide (VIP) and Peptide Histidine Methionine (PHM) in the human gastrointestinal tract was studied by in situ hybridization and Northern blotting for PHM/ VIP mRNA and immunocytochemistry using specific antisera against the bioactive Peptides PHM and VIP. In the colon sigmoideum, antisera against all five putative processing products of the VIP precursor (prepro-VIP) were used, namely prepro-VIP 22–79, PHM, prepro-VIP 111–122, VIP and prepro-VIP 156–170. Furthermore, RNA extracted from various regions of the gastrointestinal tract was examined by Northern blots and hybridization to a VIP-cDNA probe. Throughout the gastrointestinal tract, PHM/VIP mRNA was found in neurons only. Using single-or double-staining methods, we demonstrated both PHM/VIP mRNA and the corresponding Peptides PHM and VIP in the neurons. In the sigmoideum, the single-staining methods were extended to investigate whether the neurons simultaneously contained PHM/VIP mRNA and each of the five prepro-VIP-derived Peptides. Only one major band of PHM/VIP mRNA (1.9 kb) was found by Northern blotting in the tissue of the gastrointestinal tract.

  • Vasoactive intestinal polyPeptide and Peptide Histidine Methionine. Presence in human follicular fluid and effects on DNA synthesis and steroid secretion in cultured human granulosa/lutein cells.
    Human reproduction (Oxford England), 1994
    Co-Authors: S. Gräs, Jan Fahrenkrug, P. Ovesen, A.nyboe Andersen, Steen Sørensen, B. Ottesen
    Abstract:

    Vasoactive intestinal polyPeptide (VIP) and Peptide Histidine Methionine (PHM) originate from the same precursor molecule, prepro VIP. In the present study we examined the concentrations of VIP and PHM in human follicular fluid and their effects on cultured human granulosa/lutein cells. Follicular fluid and cells were obtained from patients undergoing in-vitro fertilization for tubal infertility. The concentrations of VIP and PHM in pre-ovulatory human follicular fluid were measured radioimmunochemically. Granulosa/lutein cells isolated from follicular fluid were cultured under serum-free conditions with VIP and PHM in varying concentrations (0.1, 10, 1000 nmol/l). [3H]Thymidine incorporation in the cells and oestradiol as well as progesterone concentrations in the culture medium were measured. The mean (+/- SEM) concentrations of VIP and PHM were 6.8 +/- 0.1 and 7.7 +/- 0.8 pmol/l, respectively. VIP at a concentration of 10 nmol/l caused a significant increase in [3H]thymidine incorporation, and at 1000 nmol/l a significant increase in oestradiol secretion was observed. VIP had no effect on progesterone secretion. PHM at the concentrations tested did not influence any of the activities. We conclude that VIP and PHM are present in human preovulatory follicular fluid and that VIP stimulates DNA synthesis and oestradiol secretion in cultured human granulosa/lutein cells. This indicates that VIP and perhaps PHM participate in the local nervous regulation of human ovarian function.

  • Peptide Histidine valine (PHV) is present and biologically active in the human female genital tract.
    Regulatory peptides, 1992
    Co-Authors: C. Palle, Bent Ottesen, Jan Fahrenkrug
    Abstract:

    The occurrence of vasoactive intestinal polyPeptide (VIP), Peptide Histidine Methionine (PHM) and Peptide Histidine valine (PHV) in the human female genital tract was studied by means of radioimmunoassay in combination with gel chromatography. In addition, the effect of PHV on genital smooth muscle activity was investigated in vitro and compared to that of VIP. Immunoreactive VIP, PHM and PHV were present in all regions of the human female genital tract, the highest concentrations being measured in the vagina and the uterine cervix. The Peptides displayed similar regional distribution and as expected from the structure of the VIP precursor molecule in which the examined Peptides are contained, the molar ratio of VIP to the total PHM/PHV immunoreactivity was close to 1:1. In all regions PHV constituted 50-70% of the total PHM/PHV immunoreactivity indicating that the dibasic conversion site after PHM was uncleaved. VIP and PHV were found to be equipotent relaxants of the smooth muscle from the Fallopian tube and the myometrium. The present study indicates that PHV like PHM and VIP may act as a neurotransmitter in the human female genital tract and thus participate in the local nervous control of the reproductive functions.

  • Vasoactive intestinal polyPeptide (VIP) and Peptide Histidine Methionine (PHM) in human penile corpus cavernosum tissue and circumflex veins: localization and in vitro effects.
    European journal of clinical investigation, 1992
    Co-Authors: H. J. Kirkeby, Jan Fahrenkrug, F. Holmquist, Bent Ottesen
    Abstract:

    Localization and functional effects of vasoactive intestinal polyPeptide (VIP) and Peptide Histidine Methionine (PHM), two Peptides derived from a common precursor molecule, were investigated in isolated preparations from human penile corpus cavernosum (CC) and circumflex vein (CV). VIP- and PHM-immunoreactivity (IR) was demonstrated in both CC and CV. The concentrations of VIP-IR and PHM-IR in CC tissue were 54.4 +/- 15.3, and 42.0 +/- 7.5 pmol g-1 wet weight respectively with a VIP/PHM ratio of 1.5 +/- 0.4 (mean +/- SEM). The corresponding values for CV tissues were 28.0 +/- 7.7 and 9.6 +/- 2.6 pmol g-1 wet weight with a VIP/PHM ratio of 3.1 +/- 0.4. CC and CV displayed VIP- and PHM-IR confined to nerve fibres in close relation to bundles of smooth muscle cells and blood vessels in both tissues. In vitro, VIP and PHM had no effects in unstimulated tissue preparations. Both Peptides concentration-dependently (10(-9)-10(-6) M) relaxed CC and CV preparations precontracted with 3 x 10(-6) M noradrenaline. In CC the maximum relaxant effect of VIP and PHM was 22 +/- 11% and 9 +/- 9% and in CV the corresponding values were 82 +/- 8% and 93 +/- 3% respectively. The present study supports the hypothesis of VIP and PHM as neurotransmitters and/or neuromodulators in the nervous control of penile erection.

Corinne Chadéneau - One of the best experts on this subject based on the ideXlab platform.

  • neuritogenesis induced by vasoactive intestinal Peptide pituitary adenylate cyclase activating polyPeptide and Peptide Histidine Methionine in sh sy5y cells is associated with regulated expression of cytoskeleton mrnas and proteins
    Journal of Neuroscience Research, 2004
    Co-Authors: Céline Héraud, Jean-marc Muller, Sandrine Hilairet, Jean-françois Leterrier, Corinne Chadéneau
    Abstract:

    Vasoactive intestinal Peptide (VIP) and the related Peptides pituitary adenylate cyclase-activating polyPeptide (PACAP) and Peptide Histidine Methionine (PHM) are known to regulate proliferation and/or differentiation in normal and tumoral cells. In this study, neuritogenesis in human neuroblastoma SH-SY5Y cells cultured in serum-free medium was induced by VIP, PACAP, and PHM. The establishment of this process was followed by the quantification of neurite length and branching and the expression of neurofilament mRNAs, neurofilament proteins, and other cytoskeletal protein markers of neuronal differentiation: neuron-specific MAPs and beta-tubulin III. Neurite length and branching and the expression of most markers tested were increased by VIP and PACAP in a similar, although slightly different, fashion. In contrast, neuritic elongation induced by PHM was correlated with neither an increase in branching or neurofilament mRNAs nor a clear change in the expression of cytoskeleton proteins, with the exception of the stimulation by PHM of doublecortin, a microtubule-associated marker of migrating neuroblasts. These findings are the first evidence from a human neuron-like cell line for 1) a direct regulation of the metabolism of neurofilaments by VIP and PACAP and 2) the induction by PHM of neuritic processes of an apparent immature character.

  • Neuritogenesis induced by vasoactive intestinal Peptide, pituitary adenylate cyclase‐activating polyPeptide, and Peptide Histidine Methionine in SH‐SY5y cells is associated with regulated expression of cytoskeleton mRNAs and proteins
    Journal of neuroscience research, 2003
    Co-Authors: Céline Héraud, Jean-marc Muller, Sandrine Hilairet, Jean-françois Leterrier, Corinne Chadéneau
    Abstract:

    Vasoactive intestinal Peptide (VIP) and the related Peptides pituitary adenylate cyclase-activating polyPeptide (PACAP) and Peptide Histidine Methionine (PHM) are known to regulate proliferation and/or differentiation in normal and tumoral cells. In this study, neuritogenesis in human neuroblastoma SH-SY5Y cells cultured in serum-free medium was induced by VIP, PACAP, and PHM. The establishment of this process was followed by the quantification of neurite length and branching and the expression of neurofilament mRNAs, neurofilament proteins, and other cytoskeletal protein markers of neuronal differentiation: neuron-specific MAPs and β-tubulin III. Neurite length and branching and the expression of most markers tested were increased by VIP and PACAP in a similar, although slightly different, fashion. In contrast, neuritic elongation induced by PHM was correlated with neither an increase in branching or neurofilament mRNAs nor a clear change in the expression of cytoskeleton proteins, with the exception of the stimulation by PHM of doublecortin, a microtubule-associated marker of migrating neuroblasts. These findings are the first evidence from a human neuron-like cell line for 1) a direct regulation of the metabolism of neurofilaments by VIP and PACAP and 2) the induction by PHM of neuritic processes of an apparent immature character. © 2003 Wiley-Liss, Inc.

Jean-marc Muller - One of the best experts on this subject based on the ideXlab platform.

  • Human H9 cells proliferation is differently controlled by vasoactive intestinal Peptide or Peptide Histidine Methionine: implication of a GTP-insensitive form of VPAC1 receptor.
    Journal of Neuroimmunology, 2004
    Co-Authors: Stéphanie Goursaud, Nicolas Pineau, Laetitia Becq-giraudon, Pierre Gressens, Jean-marc Muller, Thierry Janet
    Abstract:

    The proliferation of human lymphoblastoma cell line (H9) was differently stimulated by Peptide Histidine Methionine (PHM) and Vasoactive Intestinal Peptide (VIP). PHM induced a cyclic AMP (cAMP) accumulation, abolished by Adenylate Cyclase (AC) inhibitors leading to a loss of proliferative effect. VIP mitogenic activity was Pertussis toxin (PTX) sensitive and AC inhibitors insensitive. Pharmacological experiments performed on H9 membranes with or without a GTP analogue indicated expression of both GTP-insensitive and -sensitive PHM/VIP high-affinity binding sites (HA). H9 cells expressed only the VPAC1 receptor. VIP(10-28), known as a VPAC1 antagonist, bond to all GTP-insensitive PHM sites and inhibited evenly the PHM and VIP mitogenic actions. These data strongly suggested different mechanisms initiated by VIP and PHM and highlighted the key role of GTP-insensitive binding sites in the control of cell proliferation.

  • neuritogenesis induced by vasoactive intestinal Peptide pituitary adenylate cyclase activating polyPeptide and Peptide Histidine Methionine in sh sy5y cells is associated with regulated expression of cytoskeleton mrnas and proteins
    Journal of Neuroscience Research, 2004
    Co-Authors: Céline Héraud, Jean-marc Muller, Sandrine Hilairet, Jean-françois Leterrier, Corinne Chadéneau
    Abstract:

    Vasoactive intestinal Peptide (VIP) and the related Peptides pituitary adenylate cyclase-activating polyPeptide (PACAP) and Peptide Histidine Methionine (PHM) are known to regulate proliferation and/or differentiation in normal and tumoral cells. In this study, neuritogenesis in human neuroblastoma SH-SY5Y cells cultured in serum-free medium was induced by VIP, PACAP, and PHM. The establishment of this process was followed by the quantification of neurite length and branching and the expression of neurofilament mRNAs, neurofilament proteins, and other cytoskeletal protein markers of neuronal differentiation: neuron-specific MAPs and beta-tubulin III. Neurite length and branching and the expression of most markers tested were increased by VIP and PACAP in a similar, although slightly different, fashion. In contrast, neuritic elongation induced by PHM was correlated with neither an increase in branching or neurofilament mRNAs nor a clear change in the expression of cytoskeleton proteins, with the exception of the stimulation by PHM of doublecortin, a microtubule-associated marker of migrating neuroblasts. These findings are the first evidence from a human neuron-like cell line for 1) a direct regulation of the metabolism of neurofilaments by VIP and PACAP and 2) the induction by PHM of neuritic processes of an apparent immature character.

  • Neuritogenesis induced by vasoactive intestinal Peptide, pituitary adenylate cyclase‐activating polyPeptide, and Peptide Histidine Methionine in SH‐SY5y cells is associated with regulated expression of cytoskeleton mRNAs and proteins
    Journal of neuroscience research, 2003
    Co-Authors: Céline Héraud, Jean-marc Muller, Sandrine Hilairet, Jean-françois Leterrier, Corinne Chadéneau
    Abstract:

    Vasoactive intestinal Peptide (VIP) and the related Peptides pituitary adenylate cyclase-activating polyPeptide (PACAP) and Peptide Histidine Methionine (PHM) are known to regulate proliferation and/or differentiation in normal and tumoral cells. In this study, neuritogenesis in human neuroblastoma SH-SY5Y cells cultured in serum-free medium was induced by VIP, PACAP, and PHM. The establishment of this process was followed by the quantification of neurite length and branching and the expression of neurofilament mRNAs, neurofilament proteins, and other cytoskeletal protein markers of neuronal differentiation: neuron-specific MAPs and β-tubulin III. Neurite length and branching and the expression of most markers tested were increased by VIP and PACAP in a similar, although slightly different, fashion. In contrast, neuritic elongation induced by PHM was correlated with neither an increase in branching or neurofilament mRNAs nor a clear change in the expression of cytoskeleton proteins, with the exception of the stimulation by PHM of doublecortin, a microtubule-associated marker of migrating neuroblasts. These findings are the first evidence from a human neuron-like cell line for 1) a direct regulation of the metabolism of neurofilaments by VIP and PACAP and 2) the induction by PHM of neuritic processes of an apparent immature character. © 2003 Wiley-Liss, Inc.

Céline Héraud - One of the best experts on this subject based on the ideXlab platform.

  • neuritogenesis induced by vasoactive intestinal Peptide pituitary adenylate cyclase activating polyPeptide and Peptide Histidine Methionine in sh sy5y cells is associated with regulated expression of cytoskeleton mrnas and proteins
    Journal of Neuroscience Research, 2004
    Co-Authors: Céline Héraud, Jean-marc Muller, Sandrine Hilairet, Jean-françois Leterrier, Corinne Chadéneau
    Abstract:

    Vasoactive intestinal Peptide (VIP) and the related Peptides pituitary adenylate cyclase-activating polyPeptide (PACAP) and Peptide Histidine Methionine (PHM) are known to regulate proliferation and/or differentiation in normal and tumoral cells. In this study, neuritogenesis in human neuroblastoma SH-SY5Y cells cultured in serum-free medium was induced by VIP, PACAP, and PHM. The establishment of this process was followed by the quantification of neurite length and branching and the expression of neurofilament mRNAs, neurofilament proteins, and other cytoskeletal protein markers of neuronal differentiation: neuron-specific MAPs and beta-tubulin III. Neurite length and branching and the expression of most markers tested were increased by VIP and PACAP in a similar, although slightly different, fashion. In contrast, neuritic elongation induced by PHM was correlated with neither an increase in branching or neurofilament mRNAs nor a clear change in the expression of cytoskeleton proteins, with the exception of the stimulation by PHM of doublecortin, a microtubule-associated marker of migrating neuroblasts. These findings are the first evidence from a human neuron-like cell line for 1) a direct regulation of the metabolism of neurofilaments by VIP and PACAP and 2) the induction by PHM of neuritic processes of an apparent immature character.

  • Neuritogenesis induced by vasoactive intestinal Peptide, pituitary adenylate cyclase‐activating polyPeptide, and Peptide Histidine Methionine in SH‐SY5y cells is associated with regulated expression of cytoskeleton mRNAs and proteins
    Journal of neuroscience research, 2003
    Co-Authors: Céline Héraud, Jean-marc Muller, Sandrine Hilairet, Jean-françois Leterrier, Corinne Chadéneau
    Abstract:

    Vasoactive intestinal Peptide (VIP) and the related Peptides pituitary adenylate cyclase-activating polyPeptide (PACAP) and Peptide Histidine Methionine (PHM) are known to regulate proliferation and/or differentiation in normal and tumoral cells. In this study, neuritogenesis in human neuroblastoma SH-SY5Y cells cultured in serum-free medium was induced by VIP, PACAP, and PHM. The establishment of this process was followed by the quantification of neurite length and branching and the expression of neurofilament mRNAs, neurofilament proteins, and other cytoskeletal protein markers of neuronal differentiation: neuron-specific MAPs and β-tubulin III. Neurite length and branching and the expression of most markers tested were increased by VIP and PACAP in a similar, although slightly different, fashion. In contrast, neuritic elongation induced by PHM was correlated with neither an increase in branching or neurofilament mRNAs nor a clear change in the expression of cytoskeleton proteins, with the exception of the stimulation by PHM of doublecortin, a microtubule-associated marker of migrating neuroblasts. These findings are the first evidence from a human neuron-like cell line for 1) a direct regulation of the metabolism of neurofilaments by VIP and PACAP and 2) the induction by PHM of neuritic processes of an apparent immature character. © 2003 Wiley-Liss, Inc.

Hajime Watanobe - One of the best experts on this subject based on the ideXlab platform.

  • Stimulation by Peptide Histidine Methionine (PHM) of adrenocorticotropin secretion in patients with Cushing's disease: a comparison with the effect of vasoactive intestinal Peptide (VIP) and a study on the effect of combined administration of cortico
    The Journal of clinical endocrinology and metabolism, 1994
    Co-Authors: Hajime Watanobe, T Tamura
    Abstract:

    The effect of Peptide Histidine Methionine (PHM) on ACTH and cortisol secretion was examined in 12 female patients with Cushing's disease and 8 normal women. For comparison, we examined in both groups the effects of vasoactive intestinal Peptide (VIP), human (h) CRH plus PHM, and hCRH plus VIP. Each Peptide was given as an i.v. bolus in a dose of 100 micrograms, and plasma levels of ACTH and cortisol were measured before and at intervals up to 120 min after the injection. In all normal subjects, hCRH induced significant rises in ACTH (> 50% above the basal) and cortisol (> 20% above the basal), but PHM and VIP were without effect. In this group, hormonal responses after hCRH plus PHM and hCRH plus VIP were statistically indistinguishable from those after hCRH alone. Of the patients with Cushing's disease, 9 (75%) were responsive to hCRH, 5 (42%) were to VIP, and 3 (25%) were to PHM, showing significant increases in both ACTH and cortisol. All the 3 PHM responders were also responsive to VIP, and all the 5...

  • Anomalous growth hormone response to vasoactive intestinal Peptide and Peptide Histidine Methionine in patients with prolactinoma or hypothalamic hyperprolactinemia
    Neuropeptides, 1994
    Co-Authors: Hajime Watanobe, T Tamura, K. Takahashi
    Abstract:

    Abstract We examined a possible GH-releasing activity of vasoactive intestinal Peptide (VIP) and its homologous Peptide, Peptide Histidine Methionine (PHM), in 22 patients with hyperprolactinemia (HPRL) who comprised 19 cases of prolactinoma (PRLoma) and 3 cases of hypothalamic HPRL. Each patient underwent iv bolus injections of VIP (100 μg) and PHM (100 μg) on separate days, and plasma levels of GH and PRL were measured. The plasma GH response to VIP and PHM were considered positive (a paradoxical increase) when an increase over baseline of at least 50% occurred. In agreement with previous reports, the PRL-releasing activity of VIP and PHM in our patients with HPRL were subnormal. Thirteen (59%) patients showed a paradoxical rise in GH after VIP, and 4 (18%) patients did so after PHM. It is to be noted that all the 3 patients with hypothalamic HPRL responded to VIP with a significant rise in GH. 3 of the 4 PHM-responders were also responsive to VIP, which suggests that PHM may have activated VIP receptors in the pituitary of the PHM-responders as a partial agonist of the VIP receptor. The responders and nonresponders to VIP or PHM, respectively, had similar results with respect to the mean age, and the mean basal PRL and GH levels in the plasma. Since these paradoxical GH responses were observed in not only the patients with PRLoma but also those with hypothalamic HPRL, it may be that these anomalous GH responses in HPRL were due to the HPRL itself rather than due to the neoplastic lactotrophs. Although the pathophysiological significance of this phenomenon is open to question, it is suggested at least that VIP and/or PHM receptors may anomalously appear on somatotrophs in the pituitary of at least some patients with HPRL.

  • Lack of involvement of the cholinergic mechanism in vasoactive intestinal Peptide- and Peptide-Histidine Methionine-induced growth hormone(GH) responses in acromegaly: Comparison with the GH responses to thyrotropin-releasing hormone and GH-releasing
    Neuropeptides, 1994
    Co-Authors: Hajime Watanobe, Satoshi Habu, Ryo Nasushita, Kazuo Takebe
    Abstract:

    Abstract We examined whether the cholinergic mechanism is involved in the paradoxical GH responses to vasoactive intestinal Peptide (VIP) and Peptide Histidine Methionine (PHM) in acromegaly. 28 patients with active acromegaly underwent i.v. bolus injections of thyrotropin-releasing hormone (TRH, 500 μg), GH-releasing hormone (GHRH, 100 μg), VIP (100 μg), and PHM (100 μg) with or without a prior atropine treatment (1 mg, i.m., 30 min before). Blood samples were collected before and at intervals up to 120 min after the injection, and plasma GH levels were measured. In response to TRH, GHRH, VIP and PHM, 23 (82%), 24 (86%), 13 (46%) and 7 (25%) patients, respectively, responded with a significant GH increase (> 50% and 6 μg/l above the basal level). The effect of atropine pretreatment was examined in only these responders to the respective Peptides. When the GH responses were estimated by the area under the response curve, the atropine pretreatment was able to significantly suppress the GH response to GHRH, but not to TRH, VIP, or PHM. Although the lack of cholinergic involvement in the TRH-induced GH release in acromegaly is confirmatory to previous reports, the same results with the VIP- and PHM-induced GH release are novel. The present study may suggest that in acromegaly the physiological GH response is mediated by the cholinergic mechanism, but the paradoxical ones are not.

  • A further study on the stimulatory effect of Peptide Histidine Methionine on growth hormone secretion in acromegaly: a dose-related study and a comparison with vasoactive intestinal Peptide.
    Neuropeptides, 1992
    Co-Authors: Hajime Watanobe, Kazuo Takebe
    Abstract:

    Abstract We examined whether the GH-releasing effect of Peptide Histidine Methionine (PHM) in acromegaly may be mediated by activation of pituitary receptors for vasoactive intestinal Peptide (VIP), which is structurally similar to but more powerful than PHM in stimulating GH secretion in acromegaly. VIP (50 or 100 μg) or PHM (50, 100, or 200 μg) was given as an i.v. bolus to 11 patients with active acromegaly, and plasma GH levels were measured before and at intervals up to 120 min after the injection. A paradoxical GH response (>50% and >6 μg/l above the basal) to 50 or 100 μg of VIP was observed in 4 (36%) or 5 (45%) patients, respectively. 2 (18%) patients showed paradoxical GH responses to both 50 and 100 μg of PHM, and, interestingly, as many as 5 (45%) patients showed positive GH responses to 200 μg of PHM. 3 of these 5 responders to 200 μg of PHM were also responders to both doses of VIP. To add to, one of the responders to 100 μg of VIP did not show a positive GH response to even 200 μg of PHM. These results may suggest that in at least some acromegalics the PHM stimulation of GH secretion is mediated by activation of pituitary VIP receptors by PHM and/or by PHM binding to its specific receptors which may have appeared concomitantly with VIP receptors. However, the occasional heterogeneity of the VIP- and PHM-induced GH responses may suggest that on some somatotroph adenomas either VIP or PHM receptors may appear independently.

  • Paradoxical response of growth hormone to Peptide Histidine Methionine in acromegaly: comparison with the effects of thyrotropin-releasing hormone and vasoactive intestinal Peptide.
    The Journal of clinical endocrinology and metabolism, 1991
    Co-Authors: Hajime Watanobe, Shinsuke Sasaki, Ken Sone, Kazuo Takebe
    Abstract:

    We examined whether Peptide Histidine Methionine (PHM) induces a paradoxical rise in plasma GH in patients with acromegaly. PHM (100 μg) was given as an iv bolus to eight patients with active acromegaly, and plasma GH levels were measured before and at intervals up to 120 min after the injection. For comparison, the effects of TRH (500 μg) and vasoactive intestinal Peptide (VIP, 100 μg), Peptides known to paradoxically stimulate GH secretion in acromegalics, were assessed in all of the patients. A paradoxical rise (>50% above the basal) in plasma GH was observed in five patients after both TRH and VIP administrations, although TRH responders were not always VIP responders, nor did VIP responders always respond to TRH. In two patients, the GH response to PHM fulfilled the criteria of a paradoxical increase. Both of these patients were also TRH and VIP responders. These results suggest that PHM may be another hypothalamic hormone capable of paradoxically stimulating GH secretion in at least some acromegalic...