The Superovulated Rat: Its Use as a Model in Studies on the Acute Steroidogenic Effects of Luteinizing Hormone1

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Abstract
The use of superovulated rats in studies on the mechanism of the acute steroidogenic response to luteinizing hormone (LH) was investigated. Rats [24 days old] were superovulated by sequential administration of 50 IU pregnant mare serum gonadotropin and 25 IU human chorionic gonadotropin (hCG). The time after this pretreatment that the maximum acute steroidogenic response to LH could be elicited was established. As an index of this response, conversion of [4-14C]-cholesterol to [4-14C]pregnenolone and [4-14C]progesterone (side-chain cleavage (SCC) activity) was assayed in ovarian mitochondria prepared from animals which had received a s.c. injection of 10 .mu.g LH or saline vehicle 1 h prior to sacrifice. This procedure was repeated with groups of superovulated rats at increasing time intervals after the 2nd pretreatment injection. The acute steroidogenic response increased up to 6 days after the hCG injection and thereafter declined. The progesterone levels in the peripheral plasma of the rats were also highest 6 days after the hCG injection, 700 ng progesterone/ml. The same time interval (6 days) was used in all subsequent studies on superovulated rats. Stimulation of SCC activity in such mitochondrial preparations was a function of the dose of LH administered in vivo: a minimal response was achieved by the s.c. administration of 0.1 .mu.g LH, maximum response being elicited after 10 .mu.g LH. The time interval necessary for the development of this response was also established. SCC activity was significantly increased in animals killed 15 min after s.c. injection of 10 .mu.g LH; peripheral levels of progesterone were also increased within this period. LH may acutely stimulate the release of stored progesterone and increase its biosynthesis. Maximum stimulation of SCC activity occurred when the LH was given as late as 30 min before death, and the SCC activity remained raised when this interval was increased to 120 min.