{"id":{"repo_id":"rgu","oai_identifier":"oai:rgu-repository.worktribe.com:1993302"},"canonical_url":"https://search.dev.ndltd.org/etd/rgu/oai:rgu-repository.worktribe.com:1993302","repository":{"repo_id":"rgu","name":"Robert Gordon University","base_url":"https://rgu-repository.worktribe.com/oaiprovider"},"display":{"title":"Study of the pharmacological modification of neuroendocrine mechanisms controlling ovulation in the rat.","abstract":"The synthetic steroid, RMI 12,936 (17beta-hydroxy-7alpha-methyl-androst-5-en-3-one) inhibits ovulation in the rat. This study investigated the mechanism of action of the drug. The results showed that administration at or before 01:00h on proestrus blocked the preovulatory LH surge, which was restored by LHRH or oestradiol plus progesterone. Administration of oestradiol alone restored ovulation to only 43% of RMI 12,936-treated rats. The negative feedback effect of testosterone on LH release showed similar characteristics. Although RMI 12,936 was shown to be a potent androgen, the peripheral androgenic activity was found not to be correlated with its inhibitory effect on LH release. Instead, it was suggested that RMI 12,936 may act through antioestrogenic and antiprogestational activity. Investigation of the site of action revealed effects: a) at the ovarian level, inhibiting the biosynthesis of oestrogen and progesterone; b) at the adenohypophysial level, preventing full sensitization to LHRH; and c) at the hypothalamic level, inhibiting noradrenergic and tryptaminergic neurotransmission. The first two are not the main sites of antiovulatory activity, since administration of oestradiol plus progesterone - although they restore ovulation - cannot restore full sensitization, and secondly since RMI 12,936 injected into the third cerebral ventricle does not require to be transported to the ovary for effective ovulation blockade. The major site of action was therefore at the hypothalamic level, where RMI 12,936 blocks the neural signal mediated by noradrenaline and triggered by oestrogen. Based on the premise that RMI 12,936 has a similar mechanism of action to that of testosterone, it was proposed that the drug prevents full sensitization of the adenohypophysis by reducing the number of LHRH receptors. During this investigation, adenohypophysial sensitivity to LHRH altered. From observation throughout the year, a pattern emerged indicating the existence of seasonal variation in the mechanisms controlling LH release. This aspect requires further investigation.","abstract_html":"The synthetic steroid, RMI 12,936 (17beta-hydroxy-7alpha-methyl-androst-5-en-3-one) inhibits ovulation in the rat. This study investigated the mechanism of action of the drug. The results showed that administration at or before 01:00h on proestrus blocked the preovulatory LH surge, which was restored by LHRH or oestradiol plus progesterone. Administration of oestradiol alone restored ovulation to only 43% of RMI 12,936-treated rats. The negative feedback effect of testosterone on LH release showed similar characteristics. Although RMI 12,936 was shown to be a potent androgen, the peripheral androgenic activity was found not to be correlated with its inhibitory effect on LH release. Instead, it was suggested that RMI 12,936 may act through antioestrogenic and antiprogestational activity. Investigation of the site of action revealed effects: a) at the ovarian level, inhibiting the biosynthesis of oestrogen and progesterone; b) at the adenohypophysial level, preventing full sensitization to LHRH; and c) at the hypothalamic level, inhibiting noradrenergic and tryptaminergic neurotransmission. The first two are not the main sites of antiovulatory activity, since administration of oestradiol plus progesterone - although they restore ovulation - cannot restore full sensitization, and secondly since RMI 12,936 injected into the third cerebral ventricle does not require to be transported to the ovary for effective ovulation blockade. The major site of action was therefore at the hypothalamic level, where RMI 12,936 blocks the neural signal mediated by noradrenaline and triggered by oestrogen. Based on the premise that RMI 12,936 has a similar mechanism of action to that of testosterone, it was proposed that the drug prevents full sensitization of the adenohypophysis by reducing the number of LHRH receptors. During this investigation, adenohypophysial sensitivity to LHRH altered. From observation throughout the year, a pattern emerged indicating the existence of seasonal variation in the mechanisms controlling LH release. This aspect requires further investigation.","abstract_has_math":false,"creators":["Stewart, Ann Wilson"],"institution":"Robert Gordon's Institute of Technology","degree_name":"PhD","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["K.E. Kendle"],"committee_chairs":[],"committee_members":[],"year":1982,"date_issued":"1982","date_published":"1982","updated_at":"2026-07-24T04:10:06Z","subjects":["Ovulation inhibitors","Ovulation","Rats"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:rgu-repository.worktribe.com:1993302","https://doi.org/10.48526/rgu-wt-1993302"],"render_values":[{"text":"oai:rgu-repository.worktribe.com:1993302","href":null,"code":true},{"text":"https://doi.org/10.48526/rgu-wt-1993302","href":"https://doi.org/10.48526/rgu-wt-1993302","code":true}]}]},"links":{"outbound_url":"https://rgu-repository.worktribe.com/1993302/1/STEWART%201982%20Study%20of%20the%20pharmacological","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["K.E. Kendle"]},{"key":"dc:contributor.sponsor","label":"Sponsor","values":["No Funder Acknowledged (Outputs)"]},{"key":"dc:creator","label":"Author","values":["Stewart, Ann Wilson"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["1982-11-30"]},{"key":"dc:date.issued","label":"Date","values":["1982"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["Robert Gordon's Institute of Technology"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://rgu-repository.worktribe.com/output/1993302"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["PhD"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Ovulation inhibitors","Ovulation","Rats"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:rgu-repository.worktribe.com:1993302","https://doi.org/10.48526/rgu-wt-1993302"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://rgu-repository.worktribe.com/1993302/1/STEWART%201982%20Study%20of%20the%20pharmacological"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The synthetic steroid, RMI 12,936 (17beta-hydroxy-7alpha-methyl-androst-5-en-3-one) inhibits ovulation in the rat. This study investigated the mechanism of action of the drug. The results showed that administration at or before 01:00h on proestrus blocked the preovulatory LH surge, which was restored by LHRH or oestradiol plus progesterone. Administration of oestradiol alone restored ovulation to only 43% of RMI 12,936-treated rats. The negative feedback effect of testosterone on LH release showed similar characteristics. Although RMI 12,936 was shown to be a potent androgen, the peripheral androgenic activity was found not to be correlated with its inhibitory effect on LH release. Instead, it was suggested that RMI 12,936 may act through antioestrogenic and antiprogestational activity. Investigation of the site of action revealed effects: a) at the ovarian level, inhibiting the biosynthesis of oestrogen and progesterone; b) at the adenohypophysial level, preventing full sensitization to LHRH; and c) at the hypothalamic level, inhibiting noradrenergic and tryptaminergic neurotransmission. The first two are not the main sites of antiovulatory activity, since administration of oestradiol plus progesterone - although they restore ovulation - cannot restore full sensitization, and secondly since RMI 12,936 injected into the third cerebral ventricle does not require to be transported to the ovary for effective ovulation blockade. The major site of action was therefore at the hypothalamic level, where RMI 12,936 blocks the neural signal mediated by noradrenaline and triggered by oestrogen. Based on the premise that RMI 12,936 has a similar mechanism of action to that of testosterone, it was proposed that the drug prevents full sensitization of the adenohypophysis by reducing the number of LHRH receptors. During this investigation, adenohypophysial sensitivity to LHRH altered. From observation throughout the year, a pattern emerged indicating the existence of seasonal variation in the mechanisms controlling LH release. This aspect requires further investigation."]},{"key":"dc:title","label":"Title","values":["Study of the pharmacological modification of neuroendocrine mechanisms controlling ovulation in the rat."]}]}],"canonical_facts":{"dc:contributor.advisor":["K.E. Kendle"],"dc:contributor.sponsor":["No Funder Acknowledged (Outputs)"],"dc:creator":["Stewart, Ann Wilson"],"dc:date":["1982-11-30"],"dc:date.issued":["1982"],"dc:description.abstract":["The synthetic steroid, RMI 12,936 (17beta-hydroxy-7alpha-methyl-androst-5-en-3-one) inhibits ovulation in the rat. This study investigated the mechanism of action of the drug. The results showed that administration at or before 01:00h on proestrus blocked the preovulatory LH surge, which was restored by LHRH or oestradiol plus progesterone. Administration of oestradiol alone restored ovulation to only 43% of RMI 12,936-treated rats. The negative feedback effect of testosterone on LH release showed similar characteristics. Although RMI 12,936 was shown to be a potent androgen, the peripheral androgenic activity was found not to be correlated with its inhibitory effect on LH release. Instead, it was suggested that RMI 12,936 may act through antioestrogenic and antiprogestational activity. Investigation of the site of action revealed effects: a) at the ovarian level, inhibiting the biosynthesis of oestrogen and progesterone; b) at the adenohypophysial level, preventing full sensitization to LHRH; and c) at the hypothalamic level, inhibiting noradrenergic and tryptaminergic neurotransmission. The first two are not the main sites of antiovulatory activity, since administration of oestradiol plus progesterone - although they restore ovulation - cannot restore full sensitization, and secondly since RMI 12,936 injected into the third cerebral ventricle does not require to be transported to the ovary for effective ovulation blockade. The major site of action was therefore at the hypothalamic level, where RMI 12,936 blocks the neural signal mediated by noradrenaline and triggered by oestrogen. Based on the premise that RMI 12,936 has a similar mechanism of action to that of testosterone, it was proposed that the drug prevents full sensitization of the adenohypophysis by reducing the number of LHRH receptors. During this investigation, adenohypophysial sensitivity to LHRH altered. From observation throughout the year, a pattern emerged indicating the existence of seasonal variation in the mechanisms controlling LH release. This aspect requires further investigation."],"dc:identifier":["oai:rgu-repository.worktribe.com:1993302","https://doi.org/10.48526/rgu-wt-1993302"],"dc:identifier.uri":["https://rgu-repository.worktribe.com/1993302/1/STEWART%201982%20Study%20of%20the%20pharmacological"],"dc:language":["en"],"dc:publisher.institution":["Robert Gordon's Institute of Technology"],"dc:relation.isreferencedby":["https://rgu-repository.worktribe.com/output/1993302"],"dc:subject":["Ovulation inhibitors","Ovulation","Rats"],"dc:title":["Study of the pharmacological modification of neuroendocrine mechanisms controlling ovulation in the rat."],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["PhD"]},"updated_at":"2026-07-24T04:10:06Z"}