{"id":{"repo_id":"edinburgh","oai_identifier":"oai:era.ed.ac.uk:1842/29149"},"canonical_url":"https://search.dev.ndltd.org/etd/edinburgh/oai:era.ed.ac.uk:1842/29149","repository":{"repo_id":"edinburgh","name":"University of Edinburgh","base_url":"https://era.ed.ac.uk/server/oai/request"},"display":{"title":"Biochemistry of ovarian cells in vitro","abstract":"The major roles of prostaglandins of the E and F series in reproductive processes are reviewed,, The structures and bio¬ synthesis of the prostaglandins are described before discussing how prostaglandins may be involved in ovulation, luteal regression and uterine physiology in primates and non-primates. Finally the possible role(s) of prostaglandins in semen is discussed. Granulosa cells obtained from human Graafian follicles can be induced to luteinize in tissue culture, if given optimum gonadotrophic support, and so provide a convenient in vitro model of the progesterone secreting cells of the human corpus luteum. The effects of several prostaglandins, including prostaglandin F₂α (PGF₂α) and PGE₂, on progesterone production by these cells was investigated. PGF₂α„ displayed luteolytic characteristics in this in vitro system by inhibiting both basal and gonadotrophin stimulated progesterone production. In contrast, PGE₂ stimulated production of progesterone by human granulosa cells, and this stimulation was not prevented by the addition of PGF₂α . It is suggested that PGF₂α may initiate functional luteal regression in vivo by a biochemical action on the luteal cell to inhibit specifically LH activation of adenylate cyclase. This possibility was supported by in vivo studies using ewes bearing ovarian autotransplants since it was found that, just as in vitro, simultaneous administration of PGE₂ would antagonise the luteolytic action of PGF₂α. Corpora lutea were infused with either PGF₂α, PGE₂ PGE₂α + PGE₂ or saline on Day 10 of the cycle. Ovarian venous blood obtained before, during and up to 12 hours after the infusion period was assayed for progesterone. PGF₂α produced an immediate, rapid and sustained decline in progesterone secretion, but infusion of PGE₂ together with PGF₂α prevented the decline until after the infusion. Progesterone secretion was unaffected by infusion of PGE₂ alone. Oestrous behaviour was observed in 4. out of 7 animals infused with PGF₂α, but in only 1 out of 6 infused with PGF₂α + PGE₂. None of the animals infused with PGE₂ alone or saline only came into heat. Although the studies with luteinized human granulosa cells indicated that PGF₂α has the potential of being luteolytic in women, unacceptable side-effects arising from its concomitant action on smooth muscle limits its potential usefullness clinically as a \"menstrual inducer\". Some 16-aryloxy analogues of PGF₂α are potent luteolysins in laboratory and farm animals, and virtually devoid of side-effects on smooth muscle at luteolytic doses. When their effect on progesterone production by luteinized human granulosa cells in tissue culture was investigated, inhibition of both basal and gonadotrophin stimulated progesterone production was observed, so revealing characteristics expected of potential human luteolysins. The analogues were, however, unable to inhibit progesterone production stimulated by PGE₂, suggesting that like PGF₂α these compounds may act by specifically blocking LH-activated adenylate cyclase. These in vitro findings suggest clinical studies to assess the potential of 16-aryloxy analogues to act as \"menstrual inducers\" in women by causing luteal regression might be worthwhile. The newly formed corpus luteum of many species is refractory to the lytic action of PGF₂α. This phenomenon was studied utilizing luteinized porcine,bovine and human granulosa cells in tissue culture. PGF₂α readily inhibited progesterone production by cells producing low amounts of progesterone, but as the cellular capacity to synthesize progesterone rose, a decreasing ability to bind PGF₂α rendered the cells refractory to PGF₂α. Since the steroidogenic potential of the luteinized granulosa cells is related to the amount of LH bound to the cell, bound LH may protect the cell from the lytic action of PGF₂α. A \"see-saw\" type of interaction between LH and PGF₂α is postulated to account for the resistance of the newly formed corpus luteum to PGF₂α. A relatively simple technique utilizing collagenase disaggregation was found to be effective in obtaining dissociated, isolated bovine luteal cells. PGF₂α inhibited hCG- stimulated progesterone production by these cells in short-term cultures (A hours) but failed to inhibit either PGF₂ or dibutyryl cyclic AIT stimulated progesterone production. Progesterone production by the isolated luteal cells could not be sustained in long-term cultures (>1 day), which therefore limits the usefulness of these cells in in vitro studies of corpus luteum function The ability of luteinized bovine granulosa cells in tissue culture to synthesize oestrogens was examined. The cells had an active \"\\Shydroxylase enzyme system which aromatized both exogenous androstenedione and testosterone to oestradiol. In the absence of exogenous androgens, however, the cells failed to synthesize oestrogens due to their limited capacity to synthesize androgen precursor. It is suggested that the function of the theca-lutein cells, present in those corpora lutea which synthesize oestrogens, may be to provide androgen precursor for aromatization to oestrogens by the granulosa-lutein cells. Finally, luteal regression in primates and non-primates is compared, and a mechanism is proposed of how gonadotrophins and PGF₂α, between them, may regulate luteal function in non-pregnant and pregnant women.","abstract_html":"The major roles of prostaglandins of the E and F series in reproductive processes are reviewed,, The structures and bio¬ synthesis of the prostaglandins are described before discussing how prostaglandins may be involved in ovulation, luteal regression and uterine physiology in primates and non-primates. Finally the possible role(s) of prostaglandins in semen is discussed. Granulosa cells obtained from human Graafian follicles can be induced to luteinize in tissue culture, if given optimum gonadotrophic support, and so provide a convenient in vitro model of the progesterone secreting cells of the human corpus luteum. The effects of several prostaglandins, including prostaglandin F₂α (PGF₂α) and PGE₂, on progesterone production by these cells was investigated. PGF₂α„ displayed luteolytic characteristics in this in vitro system by inhibiting both basal and gonadotrophin stimulated progesterone production. In contrast, PGE₂ stimulated production of progesterone by human granulosa cells, and this stimulation was not prevented by the addition of PGF₂α . It is suggested that PGF₂α may initiate functional luteal regression in vivo by a biochemical action on the luteal cell to inhibit specifically LH activation of adenylate cyclase. This possibility was supported by in vivo studies using ewes bearing ovarian autotransplants since it was found that, just as in vitro, simultaneous administration of PGE₂ would antagonise the luteolytic action of PGF₂α. Corpora lutea were infused with either PGF₂α, PGE₂ PGE₂α + PGE₂ or saline on Day 10 of the cycle. Ovarian venous blood obtained before, during and up to 12 hours after the infusion period was assayed for progesterone. PGF₂α produced an immediate, rapid and sustained decline in progesterone secretion, but infusion of PGE₂ together with PGF₂α prevented the decline until after the infusion. Progesterone secretion was unaffected by infusion of PGE₂ alone. Oestrous behaviour was observed in 4. out of 7 animals infused with PGF₂α, but in only 1 out of 6 infused with PGF₂α + PGE₂. None of the animals infused with PGE₂ alone or saline only came into heat. Although the studies with luteinized human granulosa cells indicated that PGF₂α has the potential of being luteolytic in women, unacceptable side-effects arising from its concomitant action on smooth muscle limits its potential usefullness clinically as a "menstrual inducer". Some 16-aryloxy analogues of PGF₂α are potent luteolysins in laboratory and farm animals, and virtually devoid of side-effects on smooth muscle at luteolytic doses. When their effect on progesterone production by luteinized human granulosa cells in tissue culture was investigated, inhibition of both basal and gonadotrophin stimulated progesterone production was observed, so revealing characteristics expected of potential human luteolysins. The analogues were, however, unable to inhibit progesterone production stimulated by PGE₂, suggesting that like PGF₂α these compounds may act by specifically blocking LH-activated adenylate cyclase. These in vitro findings suggest clinical studies to assess the potential of 16-aryloxy analogues to act as "menstrual inducers" in women by causing luteal regression might be worthwhile. The newly formed corpus luteum of many species is refractory to the lytic action of PGF₂α. This phenomenon was studied utilizing luteinized porcine,bovine and human granulosa cells in tissue culture. PGF₂α readily inhibited progesterone production by cells producing low amounts of progesterone, but as the cellular capacity to synthesize progesterone rose, a decreasing ability to bind PGF₂α rendered the cells refractory to PGF₂α. Since the steroidogenic potential of the luteinized granulosa cells is related to the amount of LH bound to the cell, bound LH may protect the cell from the lytic action of PGF₂α. A "see-saw" type of interaction between LH and PGF₂α is postulated to account for the resistance of the newly formed corpus luteum to PGF₂α. A relatively simple technique utilizing collagenase disaggregation was found to be effective in obtaining dissociated, isolated bovine luteal cells. PGF₂α inhibited hCG- stimulated progesterone production by these cells in short-term cultures (A hours) but failed to inhibit either PGF₂ or dibutyryl cyclic AIT stimulated progesterone production. Progesterone production by the isolated luteal cells could not be sustained in long-term cultures (>1 day), which therefore limits the usefulness of these cells in in vitro studies of corpus luteum function The ability of luteinized bovine granulosa cells in tissue culture to synthesize oestrogens was examined. The cells had an active "\\Shydroxylase enzyme system which aromatized both exogenous androstenedione and testosterone to oestradiol. In the absence of exogenous androgens, however, the cells failed to synthesize oestrogens due to their limited capacity to synthesize androgen precursor. It is suggested that the function of the theca-lutein cells, present in those corpora lutea which synthesize oestrogens, may be to provide androgen precursor for aromatization to oestrogens by the granulosa-lutein cells. Finally, luteal regression in primates and non-primates is compared, and a mechanism is proposed of how gonadotrophins and PGF₂α, between them, may regulate luteal function in non-pregnant and pregnant women.","abstract_has_math":false,"creators":["Henderson, Keith Meade"],"institution":"The University of Edinburgh","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1977,"date_issued":"1977","date_published":"1977","updated_at":"2026-07-24T02:13:59Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1842/29149","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Henderson, Keith Meade"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2018-03-29T12:17:05Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2018-03-29T12:17:05Z"]},{"key":"dc:date.issued","label":"Date","values":["1977"]},{"key":"dc:publisher","label":"Institution","values":["The University of Edinburgh"]},{"key":"dc:type","label":"Dc Type","values":["Thesis or Dissertation"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["PhD Doctor of Philosophy"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1842/29149"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The major roles of prostaglandins of the E and F series in reproductive processes are reviewed,, The structures and bio¬ synthesis of the prostaglandins are described before discussing how prostaglandins may be involved in ovulation, luteal regression and uterine physiology in primates and non-primates. Finally the possible role(s) of prostaglandins in semen is discussed. Granulosa cells obtained from human Graafian follicles can be induced to luteinize in tissue culture, if given optimum gonadotrophic support, and so provide a convenient in vitro model of the progesterone secreting cells of the human corpus luteum. The effects of several prostaglandins, including prostaglandin F₂α (PGF₂α) and PGE₂, on progesterone production by these cells was investigated. PGF₂α„ displayed luteolytic characteristics in this in vitro system by inhibiting both basal and gonadotrophin stimulated progesterone production. In contrast, PGE₂ stimulated production of progesterone by human granulosa cells, and this stimulation was not prevented by the addition of PGF₂α . It is suggested that PGF₂α may initiate functional luteal regression in vivo by a biochemical action on the luteal cell to inhibit specifically LH activation of adenylate cyclase. This possibility was supported by in vivo studies using ewes bearing ovarian autotransplants since it was found that, just as in vitro, simultaneous administration of PGE₂ would antagonise the luteolytic action of PGF₂α. Corpora lutea were infused with either PGF₂α, PGE₂ PGE₂α + PGE₂ or saline on Day 10 of the cycle. Ovarian venous blood obtained before, during and up to 12 hours after the infusion period was assayed for progesterone. PGF₂α produced an immediate, rapid and sustained decline in progesterone secretion, but infusion of PGE₂ together with PGF₂α prevented the decline until after the infusion. Progesterone secretion was unaffected by infusion of PGE₂ alone. Oestrous behaviour was observed in 4. out of 7 animals infused with PGF₂α, but in only 1 out of 6 infused with PGF₂α + PGE₂. None of the animals infused with PGE₂ alone or saline only came into heat. Although the studies with luteinized human granulosa cells indicated that PGF₂α has the potential of being luteolytic in women, unacceptable side-effects arising from its concomitant action on smooth muscle limits its potential usefullness clinically as a \"menstrual inducer\". Some 16-aryloxy analogues of PGF₂α are potent luteolysins in laboratory and farm animals, and virtually devoid of side-effects on smooth muscle at luteolytic doses. When their effect on progesterone production by luteinized human granulosa cells in tissue culture was investigated, inhibition of both basal and gonadotrophin stimulated progesterone production was observed, so revealing characteristics expected of potential human luteolysins. The analogues were, however, unable to inhibit progesterone production stimulated by PGE₂, suggesting that like PGF₂α these compounds may act by specifically blocking LH-activated adenylate cyclase. These in vitro findings suggest clinical studies to assess the potential of 16-aryloxy analogues to act as \"menstrual inducers\" in women by causing luteal regression might be worthwhile. The newly formed corpus luteum of many species is refractory to the lytic action of PGF₂α. This phenomenon was studied utilizing luteinized porcine,bovine and human granulosa cells in tissue culture. PGF₂α readily inhibited progesterone production by cells producing low amounts of progesterone, but as the cellular capacity to synthesize progesterone rose, a decreasing ability to bind PGF₂α rendered the cells refractory to PGF₂α. Since the steroidogenic potential of the luteinized granulosa cells is related to the amount of LH bound to the cell, bound LH may protect the cell from the lytic action of PGF₂α. A \"see-saw\" type of interaction between LH and PGF₂α is postulated to account for the resistance of the newly formed corpus luteum to PGF₂α. A relatively simple technique utilizing collagenase disaggregation was found to be effective in obtaining dissociated, isolated bovine luteal cells. PGF₂α inhibited hCG- stimulated progesterone production by these cells in short-term cultures (A hours) but failed to inhibit either PGF₂ or dibutyryl cyclic AIT stimulated progesterone production. Progesterone production by the isolated luteal cells could not be sustained in long-term cultures (>1 day), which therefore limits the usefulness of these cells in in vitro studies of corpus luteum function The ability of luteinized bovine granulosa cells in tissue culture to synthesize oestrogens was examined. The cells had an active \"\\Shydroxylase enzyme system which aromatized both exogenous androstenedione and testosterone to oestradiol. In the absence of exogenous androgens, however, the cells failed to synthesize oestrogens due to their limited capacity to synthesize androgen precursor. It is suggested that the function of the theca-lutein cells, present in those corpora lutea which synthesize oestrogens, may be to provide androgen precursor for aromatization to oestrogens by the granulosa-lutein cells. Finally, luteal regression in primates and non-primates is compared, and a mechanism is proposed of how gonadotrophins and PGF₂α, between them, may regulate luteal function in non-pregnant and pregnant women."]},{"key":"dc:title","label":"Title","values":["Biochemistry of ovarian cells in vitro"]}]}],"canonical_facts":{"dc:creator":["Henderson, Keith Meade"],"dc:date.accessioned":["2018-03-29T12:17:05Z"],"dc:date.available":["2018-03-29T12:17:05Z"],"dc:date.issued":["1977"],"dc:description.abstract":["The major roles of prostaglandins of the E and F series in reproductive processes are reviewed,, The structures and bio¬ synthesis of the prostaglandins are described before discussing how prostaglandins may be involved in ovulation, luteal regression and uterine physiology in primates and non-primates. Finally the possible role(s) of prostaglandins in semen is discussed. Granulosa cells obtained from human Graafian follicles can be induced to luteinize in tissue culture, if given optimum gonadotrophic support, and so provide a convenient in vitro model of the progesterone secreting cells of the human corpus luteum. The effects of several prostaglandins, including prostaglandin F₂α (PGF₂α) and PGE₂, on progesterone production by these cells was investigated. PGF₂α„ displayed luteolytic characteristics in this in vitro system by inhibiting both basal and gonadotrophin stimulated progesterone production. In contrast, PGE₂ stimulated production of progesterone by human granulosa cells, and this stimulation was not prevented by the addition of PGF₂α . It is suggested that PGF₂α may initiate functional luteal regression in vivo by a biochemical action on the luteal cell to inhibit specifically LH activation of adenylate cyclase. This possibility was supported by in vivo studies using ewes bearing ovarian autotransplants since it was found that, just as in vitro, simultaneous administration of PGE₂ would antagonise the luteolytic action of PGF₂α. Corpora lutea were infused with either PGF₂α, PGE₂ PGE₂α + PGE₂ or saline on Day 10 of the cycle. Ovarian venous blood obtained before, during and up to 12 hours after the infusion period was assayed for progesterone. PGF₂α produced an immediate, rapid and sustained decline in progesterone secretion, but infusion of PGE₂ together with PGF₂α prevented the decline until after the infusion. Progesterone secretion was unaffected by infusion of PGE₂ alone. Oestrous behaviour was observed in 4. out of 7 animals infused with PGF₂α, but in only 1 out of 6 infused with PGF₂α + PGE₂. None of the animals infused with PGE₂ alone or saline only came into heat. Although the studies with luteinized human granulosa cells indicated that PGF₂α has the potential of being luteolytic in women, unacceptable side-effects arising from its concomitant action on smooth muscle limits its potential usefullness clinically as a \"menstrual inducer\". Some 16-aryloxy analogues of PGF₂α are potent luteolysins in laboratory and farm animals, and virtually devoid of side-effects on smooth muscle at luteolytic doses. When their effect on progesterone production by luteinized human granulosa cells in tissue culture was investigated, inhibition of both basal and gonadotrophin stimulated progesterone production was observed, so revealing characteristics expected of potential human luteolysins. The analogues were, however, unable to inhibit progesterone production stimulated by PGE₂, suggesting that like PGF₂α these compounds may act by specifically blocking LH-activated adenylate cyclase. These in vitro findings suggest clinical studies to assess the potential of 16-aryloxy analogues to act as \"menstrual inducers\" in women by causing luteal regression might be worthwhile. The newly formed corpus luteum of many species is refractory to the lytic action of PGF₂α. This phenomenon was studied utilizing luteinized porcine,bovine and human granulosa cells in tissue culture. PGF₂α readily inhibited progesterone production by cells producing low amounts of progesterone, but as the cellular capacity to synthesize progesterone rose, a decreasing ability to bind PGF₂α rendered the cells refractory to PGF₂α. Since the steroidogenic potential of the luteinized granulosa cells is related to the amount of LH bound to the cell, bound LH may protect the cell from the lytic action of PGF₂α. A \"see-saw\" type of interaction between LH and PGF₂α is postulated to account for the resistance of the newly formed corpus luteum to PGF₂α. A relatively simple technique utilizing collagenase disaggregation was found to be effective in obtaining dissociated, isolated bovine luteal cells. PGF₂α inhibited hCG- stimulated progesterone production by these cells in short-term cultures (A hours) but failed to inhibit either PGF₂ or dibutyryl cyclic AIT stimulated progesterone production. Progesterone production by the isolated luteal cells could not be sustained in long-term cultures (>1 day), which therefore limits the usefulness of these cells in in vitro studies of corpus luteum function The ability of luteinized bovine granulosa cells in tissue culture to synthesize oestrogens was examined. The cells had an active \"\\Shydroxylase enzyme system which aromatized both exogenous androstenedione and testosterone to oestradiol. In the absence of exogenous androgens, however, the cells failed to synthesize oestrogens due to their limited capacity to synthesize androgen precursor. It is suggested that the function of the theca-lutein cells, present in those corpora lutea which synthesize oestrogens, may be to provide androgen precursor for aromatization to oestrogens by the granulosa-lutein cells. Finally, luteal regression in primates and non-primates is compared, and a mechanism is proposed of how gonadotrophins and PGF₂α, between them, may regulate luteal function in non-pregnant and pregnant women."],"dc:identifier.uri":["http://hdl.handle.net/1842/29149"],"dc:publisher":["The University of Edinburgh"],"dc:title":["Biochemistry of ovarian cells in vitro"],"dc:type":["Thesis or Dissertation"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["PhD Doctor of Philosophy"]},"updated_at":"2026-07-24T02:13:59Z"}