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Gonadotropin and Gonadal Steroid Release in Response to a Gonadotropin-Releasing Hormone Agonist in G_q^ɑ and G_(11)^ɑ Knockout Mice

Stanislaus, Dinesh and Janovick, Jo Ann and Ji, Tae and Wilkie, Thomas M. and Offermanns, Stefan and Conn, Michael P. (1998) Gonadotropin and Gonadal Steroid Release in Response to a Gonadotropin-Releasing Hormone Agonist in G_q^ɑ and G_(11)^ɑ Knockout Mice. Endocrinology, 139 (6). pp. 2710-2717. ISSN 0013-7227. https://resolver.caltech.edu/CaltechAUTHORS:20170224-070728237

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Abstract

In this study, we used mice lacking the G_(11)^α[ G_(11) knockout (KO)] or G_q^α gene (G_q KO) to examine LH release in response to a metabolically stable GnRH agonist (Buserelin). Mice homozygous for the absence of G_(11)^α and G_q^α appear to breed normally. Treatment of (5 wk old) female KO mice with the GnRH agonist Buserelin (2 μg/100 μl, sc) resulted in a rapid increase of serum LH levels (reaching 328 ± 58 pg/25 μl for G_(11) KO; 739 ± 95 pg/25 μl for G_q KO) at 75 min. Similar treatment of the control strain, 129SvEvTacfBr for G_(11) KO or the heterozygous mice for G_q KO, resulted in an increase in serum LH levels (428 ± 57 pg/25 μl for G_(11) KO; 884 ± 31 pg/25 μl for G_q KO) at 75 min. Both G_(11) KO and G_q KO male mice released LH in response to Buserelin (2 μg/100 μl of vehicle; 363 ± 53 pg/25μ l and 749 ± 50 pg/25 μl 1 h after treatment, respectively). These values were not significantly different from the control strain. In a long-term experiment, Buserelin was administered every 12 h, and LH release was assayed 1 h later. In female G11 KO mice and control strain, serum LH levels reached approximately 500 pg/25 μl within the first hour, then subsided to a steady level (∼100 pg/25 μl) for 109 h. In male G_(11) KO mice and in control strain, elevated LH release lasted for 13 h; however, LH levels in the G_(11) KO male mice did not reach control levels for approximately 49 h. In a similar experimental protocol, the G_q KO male mice released less LH (531 ± 95 pg/25 μl) after 13 h from the start of treatment than the heterozygous male mice (865 ± 57 pg/25 μl), but the female KO mice released more LH (634 ± 56 pg/25 μl) after 1 h from the start of treatment than the heterozygous female mice (346 ± 63 pg/25 μl). However, after the initial LH flare, the LH levels in the heterozygous mice never reached the basal levels achieved by the KO mice. G_(11) KO mice were less sensitive to low doses (5 ng/per animal) of Buserelin than the respective control mice. Male G_(11) KO mice produced more testosterone than the control mice after 1 h of stimulation by 2 μg of Buserelin, whereas there was no significant difference in Buserelin stimulated testosterone levels between G_q KO and heterozygous control mice. There was no significant difference in Buserelin stimulated estradiol production in the female G_q KO mice compared with control groups of mice. However, female G_(11) KO mice produced less estradiol in response to Buserelin (2 μg) compared with control strain. Although there were differences in the dynamics of LH release and steroid production in response to Buserelin treatment compared with control groups of mice, the lack of complete abolition of these processes, such as stimulated LH release, and steroid production, suggests that these G proteins are either not absolutely required or are able to functionally compensate for each other.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1210/en.139.6.2710DOIArticle
https://academic.oup.com/endo/issue/139/6PublisherArticle
Additional Information:© 1998 by The Endocrine Society. Received October 29, 1997. We would like to thank Tom Kline and his colleagues at ORPRC SPF-facility for the care of the mouse colony. We would also like to thank Patti Williams for secretarial help. These studies were supported by NIH Grants HD-19899, HD-00163, HD-18185, and RR-0011257.
Funders:
Funding AgencyGrant Number
NIHHD-19899
NIHHD-00163
NIHHD-18185
NIHRR-0011257
Issue or Number:6
Record Number:CaltechAUTHORS:20170224-070728237
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170224-070728237
Official Citation:Dinesh Stanislaus, Jo Ann Janovick, Tae Ji, Thomas M. Wilkie, Stefan Offermanns, P. Michael Conn; Gonadotropin and Gonadal Steroid Release in Response to a Gonadotropin-Releasing Hormone Agonist in Gqα and G11α Knockout Mice. Endocrinology 1998; 139 (6): 2710-2717. doi: 10.1210/en.139.6.2710
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74518
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:24 Feb 2017 18:09
Last Modified:03 Oct 2019 16:39

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