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Steroid 5α-reductase reduces the conjugated double bond of particular steroids using NADPH. Human type 2 can convert testosterone to dihydrotestosterone and generate an inhibitory cofactor adduct from finasteride.

Dihydrotestosterone is the 5α-reduced steroid formed from testosterone. Reduction saturates the C4=C5 bond while retaining the C3 ketone and the other steroid functional groups.

Y91F implicates the Tyr hydroxyl, while E57Q implicates the Glu carboxylic-acid chemistry. Replacing tyrosine by phenylalanine retains an aromatic side chain but removes its hydroxyl, supporting a role for Tyr91 as a hydrogen bond donor that polarizes the steroid C3 carbonyl and stabilizes an enolate-like intermediate or transition state. Its hydroxyl could participate in a proton relay, but inactivity alone does not establish that it supplies the final proton.

Replacing a glutamate residue by glutamine approximately preserves side-chain size while replacing a titratable carboxylic acid by an amide. Loss of activity, combined with the acidic activity range, supports protonated Glu57 as a carbonyl-activating acid and possible proton donor. The two residues can cooperate to stabilize oxygen charge during reduction. The inhibitor-binding structure supports local contacts; it is not a direct picture of a testosterone transition state, and an N–H contact of the aza inhibitor need not occur in testosterone.

To distinguish these chemical roles from indirect effects, compare mutant and wild-type abundance, membrane insertion and folding, cofactor binding, and steroid binding. Measure initial rates with matched enzyme amounts and include no-enzyme and inhibitor-treated wild-type controls. If binding survives but turnover fails, the evidence for a catalytic defect is stronger. The published study combines structure, mutagenesis and modeled testosterone placement, so the proposed residue roles should be distinguished from direct observation of proton trajectories.^[ref]

The estimated intercept means that a female mouse with weight zero would have predicted mean testosterone concentration $2.56486ng/dL$ under this linear regression; zero weight is an extrapolation without a meaningful adult-mouse interpretation.

Holding sex fixed, each additional gram of weight is associated with an estimated $0.03378ng/dL$ increase in mean testosterone concentration, according to the fitted multiple linear regression.

At the same weight, male mice have an estimated mean testosterone concentration $7.12162ng/dL$ higher than female mice; the sex regression coefficient is an adjusted difference between the groups.

The interaction term estimates that the weight-associated change in mean testosterone concentration is $0.40688ng/dL$ per gram greater in males than females: the female slope is $-0.04518$ and the male slope is $-0.04518+0.40688=0.36170ng/dL$ per gram.

Use Poisson regression for the offspring count, with testosterone as a predictor. It models a nonnegative integer response through its conditional mean. If the conditional variance substantially exceeds that mean, a negative binomial regression is a possible alternative for overdispersion.

Use the log link:where $N_i$ is the offspring count and $T_i$ is testosterone concentration. This link function keeps the fitted conditional mean positive.

A one-unit increase in testosterone concentration, here $1ng/dL$, multiplies the expected offspring count by $\boxed{e^{{\beta }_T}}$ under the Poisson regression with a log link. Thus the exact percentage change in the conditional mean is $\boxed{100(e^{{\beta }_T}-1)\%}$. The regression coefficient ${\beta }_T$ itself is the change in the logarithm of the expected count, not an additive change in offspring number.

Nature Communications 11, 5430. The NADP–dihydrofinasteride structure, mutant assays and modeled testosterone placement provide complementary evidence; a trapped inhibitor is not a directly observed testosterone transition state.

Testosterone is a steroid with a conjugated C3-ketone/C4=C5 fragment. 5α-reductase adds hydride at C5 and a proton at C4 to make dihydrotestosterone.