The Experts below are selected from a list of 26118 Experts worldwide ranked by ideXlab platform
Lonnie D Shea - One of the best experts on this subject based on the ideXlab platform.
-
ligands receptors and transcription factors that mediate inter cellular and intra cellular communication during Ovarian Follicle development
Reproductive Sciences, 2020Co-Authors: Lonnie D Shea, Beatriz Penalver Bernabe, Teresa K Woodruff, Linda J BroadbeltAbstract:Reliably producing a competent oocyte entails a deeper comprehension of Ovarian Follicle maturation, a very complex process that includes meiotic maturation of the female gamete, the oocyte, together with the mitotic divisions of the hormone-producing somatic cells. In this report, we investigate murine Ovarian folliculogenesis in vivo using publicly available time-series microarrays from primordial to antral stage Follicles. Manually curated protein interaction networks were employed to identify autocrine and paracrine signaling between the oocyte and the somatic cells (granulosa and theca cells) at multiple stages of Follicle development. We established plausible protein-binding interactions between expressed genes that encode secreted factors and expressed genes that encode cellular receptors. Some computationally identified signaling interactions are well established, such as the paracrine signaling from the oocyte to the somatic cells through the oocyte-secreted growth factor Gdf9, while others are novel connections in term of Ovarian folliculogenesis, such as the possible paracrine connection from somatic-secreted factor Ntn3 to the oocyte receptor Neo1. Additionally, we identified several of the likely transcription factors that might control the dynamic transcriptome during Ovarian Follicle development, noting that the YAP/TAZ signaling pathway is very active in vivo. This novel dynamic model of signaling and regulation can be employed to generate testable hypotheses regarding Follicle development that could be validated experimentally, guiding the improvement of culture media to enhance in vitro Ovarian Follicle maturation and possibly novel therapeutic targets for reproductive diseases.
-
ligands receptors and transcription factors that mediate inter cellular and intra cellular communication during Ovarian Follicle development
bioRxiv, 2019Co-Authors: Beatriz Penalver Bernabe, Teresa K Woodruff, Linda J Broadbelt, Lonnie D SheaAbstract:SUMMARY Reliably producing a competent oocyte entails a deeper comprehension of Ovarian Follicle maturation, a very complex process that includes meiotic maturation of the female gamete, the oocyte, together with the mitotic divisions of the hormone-producing somatic cells. In this report, we investigate mice Ovarian folliculogenesis in vivo using publically available time-series microarrays from primordial to antral stage Follicles. Manually curated protein interaction networks were employed to identify autocrine and paracrine signaling between the oocyte and the somatic cells (granulosa and theca cells) and the oocyte and cumulus and mural cells at multiple stages of Follicle development. We established protein binding interactions between expressed genes that encoded secreted factors and expressed genes that encoded cellular receptors. Some of computationally identified signaling interactions are well established, such as the paracrine signaling from the oocyte to the somatic cells through the secreted oocyte growth factor Gdf9; while others are novel connections in term of Ovarian folliculogenesis, such as the possible paracrine connection from somatic secreted factor Ntn3 to the oocyte receptor Neo1. Additionally, we identify several of the likely transcription factors that might control the dynamic transcriptome during Ovarian Follicle development, noting that the YAP/TAP signaling is very active in vivo. This novel dynamic model of signaling and regulation can be employed to generate testable hypotheses regarding Follicle development, guide the improvement of culture media to enhance in vitro Ovarian Follicle maturation and possibly as novel therapeutic targets for reproductive diseases.
-
synergy of paracrine signaling during early stage mouse Ovarian Follicle development in vitro
Cellular and Molecular Bioengineering, 2018Co-Authors: Hong Zhou, Joseph T Decker, Melissa M Lemke, Claire E Tomaszweski, Lonnie D Shea, Kelly B Arnold, Ariella ShikanovAbstract:Paracrine signals, such as soluble cytokines and extracellular matrix cues, are essential for the survival and development of multicellular Ovarian Follicles. While it is well established that hydrogel-based culture systems successfully support the growth of late-stage Follicles for fertility preservation, growing small, early-stage Ovarian Follicles still proves to be challenging. We hypothesized that paracrine factors secreted from neighboring Follicles may be crucial for improving the survival of early-stage Follicles in vitro. To test our hypothesis, we investigated the bi-directional crosstalk of the paracrine signals, such as cell-secreted cytokines, sex hormones and transcription factors (TFs), in Follicles encapsulated and cultured for 12 days in alginate in groups of five (5×) and ten (10×). The differential profiles of TF activity and secretome during folliculogenesis were analyzed using TRanscriptional Activity CEllular aRray (TRACER) and data-driven multivariate modeling approach. The mechano- and oxygen-responsive TFs, NF-κB and HIF1, exhibited a unique upregulation signature in 10× Follicles. Consistently, levels of proangiogenic factors, such as VEGF-A and angiopoietin-2, were significantly higher in 10× Follicles than those in 5× Follicles, reaching 269.77 and 242.82 pg/mL on the last day of culture. The analysis of TRACER and secreted cytokines also revealed critical early interactions between cytokines and TFs, correlating with the observed phenotypical and functional differences between conditions. We identified unique signatures of synergism during successful early-stage Ovarian Follicle development. These findings bring us closer to understanding of mechanisms underlying the downstream effects of interactions between the extracellular microenvironment and early-stage folliculogenesis in vitro.
-
the in vitro regulation of Ovarian Follicle development using alginate extracellular matrix gels
Biomaterials, 2006Co-Authors: Pamela K Kreeger, Teresa K Woodruff, Jason W Deck, Lonnie D SheaAbstract:The extracellular matrix (ECM) provides a three-dimensional structure that promotes and regulates cell adhesion and provides signals that direct the cellular processes leading to tissue development. In this report, synthetic matrices that present defined ECM components were employed to investigate these signaling effects on tissue formation using Ovarian Follicle maturation as a model system. In vitro systems for Follicle culture are being developed to preserve fertility for women, and cultures were performed to test the hypothesis that the ECM regulates Follicle maturation in a manner that is dependent on both the ECM identity and the stage of Follicle development. Immature mouse Follicles were cultured within alginate-based matrices that were modified with specific ECM components (e.g., laminin) or RGD peptides. The matrix maintains the in vivo like morphology of the Follicle and provides an environment that supports Follicle development. The ECM components signal the somatic cells of the Follicle, affecting their growth and differentiation, and unexpectedly also affect the meiotic competence of the oocyte. These effects depend upon both the identity of the ECM components and the initial stage of the Follicle, indicating that the ECM is a dynamic regulator of Follicle development. The development of synthetic matrices that promote Follicle maturation to produce meiotically competent oocytes may provide a mechanism to preserve fertility, or more generally, provide design principles for scaffold-based approaches to tissue engineering.
Hakan A Berg - One of the best experts on this subject based on the ideXlab platform.
-
identification and characterization of membrane androgen receptors in the zip9 zinc transporter subfamily ii role of human zip9 in testosterone induced prostate and breast cancer cell apoptosis
Endocrinology, 2014Co-Authors: Yefei Pang, Jing Dong, Hakan A BergAbstract:Recently we discovered a cDNA in teleost Ovarian Follicle cells belonging to the zinc transporter ZIP9 subfamily encoding a protein with characteristics of a membrane androgen receptor (mAR). Here ...
-
identification and characterization of membrane androgen receptors in the zip9 zinc transporter subfamily i discovery in female atlantic croaker and evidence zip9 mediates testosterone induced apoptosis of Ovarian Follicle cells
Endocrinology, 2014Co-Authors: Hakan A Berg, Charles D Rice, Md Saydur Rahman, Jingjing DongAbstract:Rapid, cell surface-initiated, pregenomic androgen actions have been described in various vertebrate cells, but the receptors mediating these actions remain unidentified. We report here the cloning and expression of a cDNA from Atlantic croaker (Micropogonias undulatus) ovaries encoding a 33-kDa, seven-transmembrane protein with binding and signaling characteristics of a membrane androgen receptor that is unrelated to any previously described steroid receptor. Instead, croaker membrane androgen receptor has 81–93% amino acid sequence identity with zinc transporter ZIP9 (SLC39A9) subfamily members, indicating it is a ZIP9 protein. Croaker ZIP9 is expressed in gonadal tissues and in brain and is up-regulated in the ovary by reproductive hormones. Croaker ZIP9 protein is localized to plasma membranes of croaker granulosa cells and human breast cancer (SKBR-3) cells stably transfected with ZIP9. Recombinant croaker ZIP9 has a high affinity (dissociation constant, Kd, 12.7 nM), limited capacity (maximal binding capacity 2.8 nM/mg protein), displaceable, single binding site-specific for androgens, characteristic of steroid receptors. Testosterone activates a stimulatory G protein coupled to ZIP9, resulting in increased cAMP production. Testosterone promotes serum starvation-induced cell death and apoptosis in transfected cells and in croaker Ovarian Follicle cells that is associated with rapid increases in intracellular free zinc concentrations, suggesting an involvement of zinc in this nonclassical androgen action to promote apoptosis. These responses to testosterone are abrogated by treatment with ZIP9 small interfering RNA. The results provide the first evidence that zinc transporter proteins can function as specific steroid membrane receptors and indicate a previously unrecognized signaling pathway mediated by steroid receptors involving alterations in intracellular zinc.
Teresa K Woodruff - One of the best experts on this subject based on the ideXlab platform.
-
ligands receptors and transcription factors that mediate inter cellular and intra cellular communication during Ovarian Follicle development
Reproductive Sciences, 2020Co-Authors: Lonnie D Shea, Beatriz Penalver Bernabe, Teresa K Woodruff, Linda J BroadbeltAbstract:Reliably producing a competent oocyte entails a deeper comprehension of Ovarian Follicle maturation, a very complex process that includes meiotic maturation of the female gamete, the oocyte, together with the mitotic divisions of the hormone-producing somatic cells. In this report, we investigate murine Ovarian folliculogenesis in vivo using publicly available time-series microarrays from primordial to antral stage Follicles. Manually curated protein interaction networks were employed to identify autocrine and paracrine signaling between the oocyte and the somatic cells (granulosa and theca cells) at multiple stages of Follicle development. We established plausible protein-binding interactions between expressed genes that encode secreted factors and expressed genes that encode cellular receptors. Some computationally identified signaling interactions are well established, such as the paracrine signaling from the oocyte to the somatic cells through the oocyte-secreted growth factor Gdf9, while others are novel connections in term of Ovarian folliculogenesis, such as the possible paracrine connection from somatic-secreted factor Ntn3 to the oocyte receptor Neo1. Additionally, we identified several of the likely transcription factors that might control the dynamic transcriptome during Ovarian Follicle development, noting that the YAP/TAZ signaling pathway is very active in vivo. This novel dynamic model of signaling and regulation can be employed to generate testable hypotheses regarding Follicle development that could be validated experimentally, guiding the improvement of culture media to enhance in vitro Ovarian Follicle maturation and possibly novel therapeutic targets for reproductive diseases.
-
ligands receptors and transcription factors that mediate inter cellular and intra cellular communication during Ovarian Follicle development
bioRxiv, 2019Co-Authors: Beatriz Penalver Bernabe, Teresa K Woodruff, Linda J Broadbelt, Lonnie D SheaAbstract:SUMMARY Reliably producing a competent oocyte entails a deeper comprehension of Ovarian Follicle maturation, a very complex process that includes meiotic maturation of the female gamete, the oocyte, together with the mitotic divisions of the hormone-producing somatic cells. In this report, we investigate mice Ovarian folliculogenesis in vivo using publically available time-series microarrays from primordial to antral stage Follicles. Manually curated protein interaction networks were employed to identify autocrine and paracrine signaling between the oocyte and the somatic cells (granulosa and theca cells) and the oocyte and cumulus and mural cells at multiple stages of Follicle development. We established protein binding interactions between expressed genes that encoded secreted factors and expressed genes that encoded cellular receptors. Some of computationally identified signaling interactions are well established, such as the paracrine signaling from the oocyte to the somatic cells through the secreted oocyte growth factor Gdf9; while others are novel connections in term of Ovarian folliculogenesis, such as the possible paracrine connection from somatic secreted factor Ntn3 to the oocyte receptor Neo1. Additionally, we identify several of the likely transcription factors that might control the dynamic transcriptome during Ovarian Follicle development, noting that the YAP/TAP signaling is very active in vivo. This novel dynamic model of signaling and regulation can be employed to generate testable hypotheses regarding Follicle development, guide the improvement of culture media to enhance in vitro Ovarian Follicle maturation and possibly as novel therapeutic targets for reproductive diseases.
-
doxorubicin has dose dependent toxicity on mouse Ovarian Follicle development hormone secretion and oocyte maturation
Toxicological Sciences, 2017Co-Authors: Shuo Xiao, Jiyang Zhang, Mingjun Liu, Hideyuki Iwahata, Hunter B Rogers, Teresa K WoodruffAbstract:Doxorubicin (DOX), one of the most commonly used anticancer medications, has been reported to affect fertility by damaging Ovarian Follicles; however, the dose-dependent toxicity of DOX on the dynamic Follicle development and oocyte maturation has not been well-defined. Our objective is to determine the effects of human-relevant exposure levels of DOX on follicular functions across developmental time. In vitro cultured multilayered secondary mouse Follicles were treated with DOX at 0, 2, 20, 100, and 200 nM for 24 h, and Follicle development, hormone secretion, and oocyte maturation were analyzed. DOX caused dose-dependent toxicity on Follicle growth, survival, and secretion of 17β-estradiol (E2). At 200 nM, DOX induced DNA damage and apoptosis in Follicle somatic cells first and then in oocytes, which was correlated with the uptake of DOX first to the somatic cells followed by germ cells. Follicles treated with DOX at 0, 2, and 20 nM showed similar oocyte metaphase II (MII) percentages after in vitro oocyte maturation; however, 20 nM DOX significantly increased the number of MII oocytes with abnormal spindle morphology and chromosome misalignment. In an effort to harmonize the in vitro study to in vivo treatment, dose-dependent toxicity on oocyte meiotic maturation was found in 16-day-old CD-1 mice treated with DOX at 0, 0.4, 2, and 10 mg/kg, consistent with the in vitro oocyte maturation outcomes. Our study demonstrates that DOX has dose-dependent toxicity on Ovarian Follicle development, hormone secretion, and oocyte maturation, which are three key factors to support the female reproductive and endocrine functions.
-
the in vitro regulation of Ovarian Follicle development using alginate extracellular matrix gels
Biomaterials, 2006Co-Authors: Pamela K Kreeger, Teresa K Woodruff, Jason W Deck, Lonnie D SheaAbstract:The extracellular matrix (ECM) provides a three-dimensional structure that promotes and regulates cell adhesion and provides signals that direct the cellular processes leading to tissue development. In this report, synthetic matrices that present defined ECM components were employed to investigate these signaling effects on tissue formation using Ovarian Follicle maturation as a model system. In vitro systems for Follicle culture are being developed to preserve fertility for women, and cultures were performed to test the hypothesis that the ECM regulates Follicle maturation in a manner that is dependent on both the ECM identity and the stage of Follicle development. Immature mouse Follicles were cultured within alginate-based matrices that were modified with specific ECM components (e.g., laminin) or RGD peptides. The matrix maintains the in vivo like morphology of the Follicle and provides an environment that supports Follicle development. The ECM components signal the somatic cells of the Follicle, affecting their growth and differentiation, and unexpectedly also affect the meiotic competence of the oocyte. These effects depend upon both the identity of the ECM components and the initial stage of the Follicle, indicating that the ECM is a dynamic regulator of Follicle development. The development of synthetic matrices that promote Follicle maturation to produce meiotically competent oocytes may provide a mechanism to preserve fertility, or more generally, provide design principles for scaffold-based approaches to tissue engineering.
Yoshitaka Nagahama - One of the best experts on this subject based on the ideXlab platform.
-
participation of gs proteins in the action of relaxin like gonad stimulating substance gss for 1 methyladenine production in starfish Ovarian Follicle cells
General and Comparative Endocrinology, 2012Co-Authors: Masatoshi Mita, Kazutoshi Yamamoto, Miho Watanabe, Yuki Takeshige, Masaru Nakamura, Yoshitaka NagahamaAbstract:Gonad-stimulating substance (GSS) in starfish is the only known invertebrate peptide hormone responsible for final gamete maturation, rendering it functionally analogous to gonadotropins in vertebrates. Recently, we purified GSS from radial nerves in the starfish Asterina pectinifera and identified the chemical structure as a heterodimer composed of two different peptides (A- and B-chain) with disulfide cross-linkages. This study examined the hormonal action of GSS on Ovarian Follicle cells obtained from ovaries in growing (stage IV) and fully grown (stage V) stages, and particularly the mode of signal transduction. The action of GSS on 1-MeAde production by Follicle cells in stage V was mediated through the production of cAMP. In contrast, GSS failed to induce 1-MeAde and cAMP production by Follicle cells in stage IV. According to competitive experiments using radioiodinated and radioinert GSS, highly specific binding was observed in Follicle cells, though their affinities and numbers in stage IV were inferior to those in stage V. Interestingly, Gsα was not detected immunologically in Follicle cell membranes of stage IV. Gβ was also faint in stage IV. Although adenylyl cyclase activity in stage V was dose-dependently activated by GSS in the presence of GTP, neither GSS in the presence of GTP nor nonhydrolyzable GTP analogs were effective on the activity in stage IV. These findings strongly suggest that the failure of GSS to produce 1-MeAde is because of a lack of Gs-proteins in Follicle cells at stage IV.
-
Interaction of relaxin-like gonad-stimulating substance with Ovarian Follicle cells of the starfish Asterina pectinifera.
Zoological science, 2011Co-Authors: Masatoshi Mita, Kazutoshi Yamamoto, Yoshitaka NagahamaAbstract:Previously, gonad-stimulating substance (GSS), which acts as a gonadotropin, was purified from radial nerves of the starfish Asterina pectinifera and its structure was elucidated. Here, the interaction of GSS with receptors was examined in Ovarian Follicle cells, a target of GSS. In competitive experiments using radioiodinated and radioinert GSS, highly specific binding was observed in the microsomal/plasma membrane fraction of Follicle cells. GSS scarcely bound in the cytosolic fraction. Scatchard plots showed the numbers of binding sites (NBS) in whole homogenate and the crude membrane to be 1.65 and 3.42 pmoles/mg protein, respectively. Dissociation constant (K d) values in these two preparations were almost the same at about 0.6–0.7 nM. Furthermore, it was shown that GSS stimulated adenylyl cyclase activity in Follicle cell membranes in a dose-dependent manner that required GTP. Immunoblotting with specific antibodies for G-protein subunits after SDS-PAGE of the membrane preparation showed both stimul...
-
ecto atp diphosphohydrolase apyrase in Ovarian Follicle cells of starfish asterina pectinifera
Comparative Biochemistry and Physiology B, 1998Co-Authors: Masatoshi Mita, Michiyasu Yoshikuni, Yoshitaka NagahamaAbstract:A Mg2+-dependent ecto-ATP diphosphohydrolase (ATPDase, EC 3.6.1.5) was present in starfish Ovarian Follicle cells. The enzyme which had an optimum pH between 6.0 and 7.5 could hydrolyze triphosphonucleosides (ATP, dATP, GTP, CTP, UTP and ITP) and diphosphonucleosides (ADP, dADP, GDP, CDP, UDP and IDP), but not monophosphonucleosides. The Km values for ATP and ADP were 0.17 and 0.20 mM, respectively. The ATPDase activity was insensitive to specific ATPase inhibitors, such as ouabain, vanadate and oligomycin, an adenylate kinase inhibitor, P1, P5-di-(adenosine-5′)pentaphosphate, and a phosphodiesterase inhibitor, 1-isobutyl-3-methylxanthine. The activity was mostly distributed in the membrane fraction of Follicle cells. It is also interesting that hydrolysis of ATP and ADP occurred upon incubation of intact cells in seawater. Among various kinds of detergents, digitonin was capable of solubilizing the enzyme from the membrane fraction. Using digitonin extract, a high-performance liquid chromatography with Superose 6 column showed that the molecular weight of ecto-ATPDase in starfish Follicle cells was ∼60 000.
Masatoshi Mita - One of the best experts on this subject based on the ideXlab platform.
-
participation of gs proteins in the action of relaxin like gonad stimulating substance gss for 1 methyladenine production in starfish Ovarian Follicle cells
General and Comparative Endocrinology, 2012Co-Authors: Masatoshi Mita, Kazutoshi Yamamoto, Miho Watanabe, Yuki Takeshige, Masaru Nakamura, Yoshitaka NagahamaAbstract:Gonad-stimulating substance (GSS) in starfish is the only known invertebrate peptide hormone responsible for final gamete maturation, rendering it functionally analogous to gonadotropins in vertebrates. Recently, we purified GSS from radial nerves in the starfish Asterina pectinifera and identified the chemical structure as a heterodimer composed of two different peptides (A- and B-chain) with disulfide cross-linkages. This study examined the hormonal action of GSS on Ovarian Follicle cells obtained from ovaries in growing (stage IV) and fully grown (stage V) stages, and particularly the mode of signal transduction. The action of GSS on 1-MeAde production by Follicle cells in stage V was mediated through the production of cAMP. In contrast, GSS failed to induce 1-MeAde and cAMP production by Follicle cells in stage IV. According to competitive experiments using radioiodinated and radioinert GSS, highly specific binding was observed in Follicle cells, though their affinities and numbers in stage IV were inferior to those in stage V. Interestingly, Gsα was not detected immunologically in Follicle cell membranes of stage IV. Gβ was also faint in stage IV. Although adenylyl cyclase activity in stage V was dose-dependently activated by GSS in the presence of GTP, neither GSS in the presence of GTP nor nonhydrolyzable GTP analogs were effective on the activity in stage IV. These findings strongly suggest that the failure of GSS to produce 1-MeAde is because of a lack of Gs-proteins in Follicle cells at stage IV.
-
Interaction of relaxin-like gonad-stimulating substance with Ovarian Follicle cells of the starfish Asterina pectinifera.
Zoological science, 2011Co-Authors: Masatoshi Mita, Kazutoshi Yamamoto, Yoshitaka NagahamaAbstract:Previously, gonad-stimulating substance (GSS), which acts as a gonadotropin, was purified from radial nerves of the starfish Asterina pectinifera and its structure was elucidated. Here, the interaction of GSS with receptors was examined in Ovarian Follicle cells, a target of GSS. In competitive experiments using radioiodinated and radioinert GSS, highly specific binding was observed in the microsomal/plasma membrane fraction of Follicle cells. GSS scarcely bound in the cytosolic fraction. Scatchard plots showed the numbers of binding sites (NBS) in whole homogenate and the crude membrane to be 1.65 and 3.42 pmoles/mg protein, respectively. Dissociation constant (K d) values in these two preparations were almost the same at about 0.6–0.7 nM. Furthermore, it was shown that GSS stimulated adenylyl cyclase activity in Follicle cell membranes in a dose-dependent manner that required GTP. Immunoblotting with specific antibodies for G-protein subunits after SDS-PAGE of the membrane preparation showed both stimul...
-
ecto atp diphosphohydrolase apyrase in Ovarian Follicle cells of starfish asterina pectinifera
Comparative Biochemistry and Physiology B, 1998Co-Authors: Masatoshi Mita, Michiyasu Yoshikuni, Yoshitaka NagahamaAbstract:A Mg2+-dependent ecto-ATP diphosphohydrolase (ATPDase, EC 3.6.1.5) was present in starfish Ovarian Follicle cells. The enzyme which had an optimum pH between 6.0 and 7.5 could hydrolyze triphosphonucleosides (ATP, dATP, GTP, CTP, UTP and ITP) and diphosphonucleosides (ADP, dADP, GDP, CDP, UDP and IDP), but not monophosphonucleosides. The Km values for ATP and ADP were 0.17 and 0.20 mM, respectively. The ATPDase activity was insensitive to specific ATPase inhibitors, such as ouabain, vanadate and oligomycin, an adenylate kinase inhibitor, P1, P5-di-(adenosine-5′)pentaphosphate, and a phosphodiesterase inhibitor, 1-isobutyl-3-methylxanthine. The activity was mostly distributed in the membrane fraction of Follicle cells. It is also interesting that hydrolysis of ATP and ADP occurred upon incubation of intact cells in seawater. Among various kinds of detergents, digitonin was capable of solubilizing the enzyme from the membrane fraction. Using digitonin extract, a high-performance liquid chromatography with Superose 6 column showed that the molecular weight of ecto-ATPDase in starfish Follicle cells was ∼60 000.
-
involvement of cyclic adenosine 3 5 monophosphate in methylation during 1 methyladenine production by starfish Ovarian Follicle cells
Invertebrate Reproduction & Development, 1992Co-Authors: Masatoshi MitaAbstract:Summary Resumption of meiosis in starfish oocytes is induced by 1-methyladenine (1-MeAde) produced by Ovarian Follicle cells under the influence of a gonad-stimulating substance (GSS). With respect to 1-MeAde production by Follicle cells of the starfish, Asterina pectinifera, (1) the action of GSS is initiated by a receptor mediated activation of G-proteins, resulting in the activation of adenylate cyclase and cyclic AMP (cAMP) formation; (2) 1-MeAde produced under the influence of GSS is not prestored within the Follicle cells but is newly synthesized from a 1-MeAde precursor; (3) AMP plays an important role in the process of methylation during 1-MeAde biosynthesis induced by GSS.