W. Leroy Heinrichs

Estrogenic behavior of 2(o-chlorophenyl)-2-(p-chlorophenyl)-1,1,1-trichloroethane and its homologues

Abstract Eight chlorinated hydrocarbons were tested for their ability to compete with 3 H-estradiol-17β for specific binding proteins in uterine cytoplasm from immature rats. The binding was assayed on 5–20% sucrose density gradients. 2( o -Chlorophenyl)-1,1,1-trichloroethane (o,p′-DDT) and 2( o -chlorophenyl)-2-( p -chloropenyl)-1,1-dichloroethylene (o,p′-DDE) (1·4 × 10 −4 M) competed with 3 H-estradiol-17β (8·7 × 10 −9 M) for binding to the “8 S receptor” in the cytomplasm. 2,2-Bis-( p -chlorophenyl)-1,1,1-trichloroethane (p,p′-DDT), 2,2-bis-( p -chlorophenyl)-1,1-dichloroethylene (p,p′-DDE), 2,2-bis-( p -chlorophenyl)-1,1-dichloroethane (p,p′-DDD), 2( m -chlorophenyl)-2-( p -chlorophenyl)-1,1-dichloroethane (m,p′-DDD), 2( o -chlorophenyl)-2-( p -chlorophenyl)-1,1-dichloroethylene (o,p′-DDD) and bis-( p -chlorophenyl)-1,1-dichloroacetate (DDA) did not compete at 1sd4 × 10 −4 M. Transfer of the receptor-bound compounds into the nuclei was examined using similar competition techniques. o,p′-DDT and o,p′-DDE competed with estradiol binding in the nuclei. These studies indicate that o,p′-DDT and o,p′-DDE at high concentrations act as estrogens as measured by their ability to compete with estradiol-17β for binding to the uterine cytopoasmic receptor and in the transfer and binding of estradiol in the nuclei of uterine cells.

Differentiation of sex steroid-binding protein in adult rhesus monkeys☆☆☆★

Several species of primates have sex differences in sex steroid-binding protein (SBP), female adults having higher serum binding capacities (micrograms of dihydrotestosterone bound per deciliter) than male adults, e.g., male humans, 1.28 +/- 0.4; human females, 2.86 +4- 0.9; Macaca nemestrina male animals, 5.62 +/- 1.24; Macaca nemestrina female animals, 11.07 +/- 1.85 (means +/- standard deviations). SBP correlates inversely with metabolic clearance rates of testosterone (T). The sex difference was identified in rhesus monkeys, six per group, evaluated 4 years after postpubertal castration: male animals 3.95 +/- 1.14; female animals 5.85 +/- 0.98 (p less than 0.05). Estradiol-17 beta (E2) pellets producing physiologic levels of E2 in female monkeys obliterated the sex difference by increasing SBP in male animals. After withdrawal of E2, physiologic levels of T in male monkeys produced a marked decrease in SBP levels (p less than 0.01), and the sex difference reappeared; castrated female animals and prenatally androgenized female animals responded similarly to T (2.81 +/- 0.81 and 2.64 +/- 0.49, respectively). Both values were greater (p less than 0.05) than that of the male group (2.02 +/- 0.33). These data suggest that the sex steroid milieu influences the binding capacity of SBP for potent androgens in adulthood but that the differentiation of the SBP sex in rhesus monkeys is determined by factors other than prenatal androgen exposure.

Peripheral control of hormone metabolism

Abstract The presence of 5α-reductase and 20α-hydroxysteroid dehydrogenase has been demonstrated in brain from two species (rat and baboon). Under the conditions of the present experimental design, there appear to be significant differences related to sex and species but not to age. Our data, supported by observations of others, suggest a regulatory role of these enzymes in the control of feedback mechanisms.

Perturbations of the human menstrual cycle by oxymetholone

The luteolytic activity of oxymetholone, and anabolic steroid, has been evaluated in 10 women. Administration early in the follicular phase of the cycle inhibited ovulation and prolonged the duration of the cycles in 2 of 3 subjects, but treatment beginning on Day 10 (3 subjects) did not prevent ovulation, although subsequent plasma progesterone concentrations were reduced. Treatment after ovulation (4 subjects) suppressed progesterone levels by 50 to 80 per cent and shortened cycle length by 6 to 8 days. Side effects were weight gain and bromosulfophthalein retention. The most likely mechanisms producing these perturbations are the inhibition of luteinizing hormone release early in the cycle and, later, inhibition of progesterone biosynthesis.

Estrogen-induced proteins of human endometrium.

Abstract Estrogen-induced protein(s) in human endometrium are described. Conjugated estrogens (Premarin) and 17β-estradiol were utilized for in vivo , in situ and in vitro induction protocols in women undergoing gynecologic surgery. Differential incorporations of radiolabelled aminoacids ([ 3 H] or [ 14 C] leucine), demonstrable by polyacrylamide disc gel electrophoresis, indicated the presence of rapidly synthesized cytoplasmic protein(s) in response to estrogen exposure. Actinomycin D prevented the induction when present in the in vitro incubations, suggesting that RNA synthesis is necessary for the protein(s) to appear. The full interaction between estrogens and the human endometrial cell deserves close attention in the light of a growing concern about the role of estrogens in the induction of endometrial neoplasia.