In Vivo Effect of Pituitary Adenylate Cyclase Activating Polypeptide 38 (PACAP 38) on the Secretion of Luteinizing Hormone (LH) in Male Rats.

Osuga, Yutaka; Mitsuhashi, Naoki; Mizuno, Masahiko

doi:10.1507/endocrj1954.39.153

Cited by 59 publications

(36 citation statements)

References 13 publications

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“…There are two main explanations for the lack of high levels of LH expected in primary hypogonadism: (i) residual testosterone, although low, could still be high enough to ensure negative pituitary feedback, and (ii) the normal levels of LH, given the low testosterone values, are actually inappropriately low, giving credence to the concept that PACAP may stimulate LH release in vivo as suggested in ref. 18. In this context, the absence of PACAP prevents the appropriate and expected surge in LH levels in the context of testosterone deficiency in PACAP Ϫ/Ϫ mice.…”

Section: Discussionmentioning

confidence: 97%

“…The neuropeptide PACAP has been implicated in regulation of testosterone level in cultured Leydig cells (20)(21)(22)29). It has also been shown to potentially enhance the release of LH in vivo (18). PACAP, acting on PAC1 receptors that efficiently enhance cAMP production and intracellular calcium mobilization was shown to directly interact with many cell types, such as gonadotrope, Leydig, germ, and Sertoli cells (16).…”

Section: Discussionmentioning

confidence: 99%

“…Because PACAP is a well known endogenous stimulator of cAMP production in many cellular systems (16), and cAMP is a key compound in activation of steroidogenesis (17), this peptide is a good candidate for a regulator of Leydig cell function. Moreover, PACAP has been shown to regulate pituitary LH secretion (18). PACAP and its mRNA, detected by immunohistochemistry and in situ hybridization in testes, is expressed in the germ cell lineage, including spermatogonia, primary spermatocytes, and round spermatids, but is not expressed in Sertoli or Leydig cells (19), suggesting that germ cell PACAP may act in a paracrine fashion on PAC1 receptor-expressing Leydig cells.…”

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confidence: 99%

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Delayed testicular aging in pituitary adenylate cyclase-activating peptide (PACAP) null mice

Lacombe¹,

Lelièvre

Roselli

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Age-related decline in male sex hormones is a direct consequence of testicular aging. These changes in the hormonal complement cause physiological disturbances affecting the quality of life for millions of aging men. To assess the influence on testicular aging of pituitary adenylate cyclase-activating peptide (PACAP), a polypeptide that regulates testicular steroidogenesis in vitro, we compared the testicular structure and function between C57BL͞6 wild-type and PACAP ؊/؊ male mice, at 4 and 15 months of age. We show that, in 4-month-old PACAP ؊/؊ mice, steroidogenesis (evaluated by levels of testosterone, steroidogenic acute regulatory protein, 3␤-hydroxysteroid dehydrogenase, and P450c17) was impaired. However, the testicular structure of these animals was not affected. At 15 months of age, wild-type testis displayed typical signs of aging (patchy seminiferous tubules, germ cell depletion, and vacuolization), whereas testicular structure was remarkably well conserved in PACAP ؊/؊ animals. The depletion of germ cells found in wild-type animals was associated with a higher content of peroxynitrites, a marker of reactive oxygen species, and a higher number of apoptotic cells compared with PACAP ؊/؊ mice. Our results show that testicular aging is delayed in PACAP ؊/؊ animals. Because the expression levels of steroidogenic factors are low and constant over time in knockout animals, a proposed mechanism for the protection against testicular degeneration is that production of reactive oxygen species, a byproduct of steroidogenesis that induces apoptosis, is down-regulated in PACAP ؊/؊ animals.Leydig cells ͉ reactive oxygen species ͉ steroidogenesis ͉ neuropeptide ͉ andropause

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Delayed testicular aging in pituitary adenylate cyclase-activating peptide (PACAP) null mice

Lacombe¹,

Lelièvre

Roselli

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…In accordance with this possibility, we have previously described that estradiol and progesterone modulate LH secretion from gonadotrophs in response to other agonists that activate phospholipase C such as endothelin (36). The fact that gonadal steroids exert stimulatory and inhibitory actions on PACAP-stimulated LH release might explain the controversial data of in vivo studies on the ability of PACAP to induce gonadotropin secretion (19,(37)(38)(39).…”

Section: European Journal Of Endocrinology (1999) 140mentioning

confidence: 99%

Interactions of ovarian steroids with pituitary adenylate cyclase-activating polypeptide and GnRH in anterior pituitary cells

Ortmann

Asmus²,

Diedrich³

et al. 1999

European Journal of Endocrinology

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Pituitary adenylate cyclase-activating polypeptide (PACAP) releases LH and FSH from anterior pituitary cells. Although this effect is relatively weak, it has a strong sensitizing action on GnRHinduced gonadotropin secretion. Here we investigated the possibility that ovarian steroids, which are well-known modulators of LH secretion, interact with PACAP and GnRH in pituitary gonadotrophs. Rat pituitary cells were treated for 48 h with vehicle,

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“…VPAC-1 and VPAC-2 bind equally PACAP and VIP, and are almost exclusively coupled to adenylate cyclase (Spengler et al 1993, Rawling & Hezareh 1996, Jaworski & Proctor 2000. The expression of PACAP and its receptors can be found in many tissues, including hypothalamus, pituitary, testis and ovary (Vaudry et al 2000), and the role of PACAP in reproduction has been suggested by studies showing its involvement in the synthesis and release of gonadotropins in pituitary cells in vivo and in vitro (Hart et al 1992, Osuga et al 1992, Perrin et al 1993.…”

Section: Introductionmentioning

confidence: 99%

Gonadotropin-dependent regulation of bovine pituitary adenylate cyclase-activating polypeptide in ovarian follicles prior to ovulation

Sayasith

Brown²,

Sirois³

2007

Reproduction

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To study the regulation of bovine pituitary adenylate cyclase-activating polypeptide (PACAP) in preovulatory follicles prior to ovulation, PACAP cDNA was isolated by RT-PCR. Its open reading frame (ORF) is composed of 531 bp, and encodes for a 176-amino acid protein that bears 76-90% identity with other PACAP homologs. Using bovine preovulatory follicles obtained between 0 and 24 h after human chorionic gonadotropin (hCG) and semiquantitative RT-PCR/Southern blot, we demonstrate that levels of PACAP mRNA were low at 0 h, markedly increased at 6 and 12 h (P!0.05), and declined 18 and 24 h after hCG. Levels of PACAP mRNA were high in the bovine pituitary, testis, intestine and uterus, but moderate to low in other tissues. Analyses performed on isolated preparations of granulosa and theca cells showed a significant increase of PACAP transcripts in both cell types after hCG, whereas primary granulosa cell cultures revealed high levels of PACAP as well as its receptors PAC-1 and VPAC-2 mRNA after forskolin treatment. Overexpression of the catalytic subunit of protein kinase A (PKA) in granulosa cells stimulated, but treatment with H89 or PKA inhibitor protein inhibited PACAP mRNA expression, whereas PACAP overexpression stimulated an increase in abundance of transcripts for PGHS-2, PGES, EP2 receptor, progesterone receptor, and ADAMTS-1, but not for P450-side chain cleavage and P450 aromatase. Thus, this study demonstrates the gonadotropin-dependent regulation of PACAP mRNA in bovine preovulatory follicles, the importance of PKA activation in the expression of PACAP in granulosa cells, and stimulating effect of PACAP on gene expression during the ovulatory process. Reproduction (2007) 133 441-453

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In Vivo Effect of Pituitary Adenylate Cyclase Activating Polypeptide 38 (PACAP 38) on the Secretion of Luteinizing Hormone (LH) in Male Rats.

Cited by 59 publications

References 13 publications

Delayed testicular aging in pituitary adenylate cyclase-activating peptide (PACAP) null mice

Delayed testicular aging in pituitary adenylate cyclase-activating peptide (PACAP) null mice

Interactions of ovarian steroids with pituitary adenylate cyclase-activating polypeptide and GnRH in anterior pituitary cells

Gonadotropin-dependent regulation of bovine pituitary adenylate cyclase-activating polypeptide in ovarian follicles prior to ovulation

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