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SENSE AND ANTISENSIBILITY

The steroids estrogen and progesterone modulate sexual behaviour in rats. When ovariectomised rats primed with estrogen are injected with progesterone, they demonstrate sexual behaviour in the presence of their male counterparts. One index of this activity is the Lordosis Quotient. A study by Mani et al (1994) tested the ability of antisense oligonucleotides to the progesterone receptor to alter these responses. They compared the effects of their oligonucleotides (ODNs) with standard progesterone receptor antagonists. Data from their paper (Endocrinology 135:1409, 1994) has been abstracted in the table shown below:

Conditions:	Lordosis Quotient (LQ)
Study 1
E	10
E + P	100
E + P + RU3846	< 5
E + P + ZK98299	< 3
Study 2
E	< 5
E + P	90
E + P + Antisense ODN	< 5
E + P + Sense ODN	88

E - Estrogen, P - Progesterone. RU3846, ZK98299 are progesterone antagonists. Both ODNs were administered in a dose of 4.0 nmoles.

Comments:

Here again published data have been reformatted to provide a problem for "solution". A number of key words and phrases have been thrown in. Students acquire not only information about steroid receptors (especially estrogen and progesterone), but also learn about the "physiology" of estrus. The problem also serves to introduce students to antisense therapeutics, an emerging field in pharmacology.