Céline Martel

ALMOST EXCLUSIVE ANDROGENIC ACTION OF DEHYDROEPIANDROSTERONE IN THE RAT MAMMARY GLAND

To determine the relative role of the androgenic and/or estrogenic components of the action of dehydroepiandrosterone (DHEA) on the histomorphology and structure of the rat mammary gland, ovariectomized (OVX) female animals received DHEA administered alone or in combination with the pure antiandrogen flutamide or the pure antiestrogen EM-800 for 12 months. We have also evaluated the effect of estradiol (E2) and dihydrotestosterone constantly released from SILASTIC brand silicon implants as well as medroxyprogesterone acetate released from poly(lactide-co-glycolide) microspheres. While 1-yr OVX resulted in a severe atrophy of the mammary gland, treatment of OVX animals with DHEA stimulated lobuloalveolar and ductal growth, as well as the secretory activity of the acinar cells, thus resulting in a lobuloalveolar type of development of the mammary gland. The addition of FLU to DHEA almost completely prevented the stimulatory effect observed with DHEA alone, whereas addition of the antiestrogen EM-800 had no ...

Rapid modulation of ovarian 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase gene expression by prolactin and human chorionic gonadotropin in the hypophysectomized rat

Abstract In order to better understand the role of prolactin (PRL) and luteinizing hormone (LH) on progesterone biosynthesis in the ovary, we have investigated the time course (1–9 days) of the effect of PRL and human chorionic gonadotropin (hCG) on ovarian 3β-hydroxysteroid dehydrogenase/ Δ 5 - Δ 4 isomerase (3β-HSD) expression in the hypophysectomized rat. As evaluated by quantitative in situ hybridization using a 35 S labelled type I 3β-HSD cDNA probe, the administration of hCG for 2, 3 and 9 days induced increases of 63%, 145% and 146% above control, respectively, in 3β-HSD mRNA levels in ovarian interstitial cells. The absence of apparent effect of the gonadotropin in other ovarian cell types could explain the small modulation of ovarian 3β-HSD protein content and enzymatic activity observed in total ovarian tissue. On the other hand, treatment with PRL caused a rapid decrease in 3β-HSD mRNA levels in corpus luteum by 23%, 63%, 76% and 78% ( P 14 C]dehydroepiandrosterone into [ 14 C]androstenedione. The inhibitory effect of PRL on 3β-HSD expression and activity is correlated with a progressive decrease in serum progesterone concentration from a pretreatment value of 4.8 nM to levels below the limit of detection (

Effects of human chorionic gonadotropin (hCG) and prolactin (PRL) on 3β-hydroxy-5-ene-steroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) expression and activity in the rat ovary☆

Abstract Using a recently cloned rat ovary 3β-HSD cDNA and antibodies raised against purified human placental 3β-HSD, we have studied the effects of treatment with human chorionic gonadotropin (hCG) and hyperprolactinemia achieved by pituitary implants, alone or in combination, on the expression and activity of ovarian 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) in intact adult rats. 32P-and 35S-labeled cDNA probes were used to evaluate the effects of treatments on 3β-HSD mRNA levels by dot blot and in situ hybridization, respectively, while enzymatic activity was measured by the conversion of [14C]dehydroepiandrosterone into [14C]androstenedione. The present data show that hCG exerts a marked trophic effect on rat corpora lutea with an increase in total ovarian 3β-HSD mRNA levels, 3β-HSD protein content as well as enzymatic activity, resulting in an increase in serum progesterone levels. Prolactin-secreting pituitary implants alone, on the other hand, while exerting small effects on 3β-HSD expression and activity, led to a marked potentiation of the stimulatory effect of hCG on all parameters. The present data show that hCG and PRL act synergistically to stimulate ovarian progesterone secretion via an increase in 3β-HSD mRNA levels, protein content and enzymatic activity.

Structure and Control of Expression of the 3βHSD and 17βHSD Genes in Classical Steroidogenic and Peripheral Intracrine Tissues

It is remarkable that humans, in addition to possessing a highly sophisticated endocrine system, have largely vested sex steroid formation in peripheral tissues (1). In fact, while the ovaries and testes are the exclusive sources of androgens and estrogens in the lower mammals, the situation is very different in higher primates, where active sex steroids are in a large part or whole synthesized locally, thus providing autonomous control to target tissues that are thus able to adjust formation and metabolism of sex steroids to local requirements. The situation of a high secretion rate of adrenal precursor sex steroids in men and women is thus completely different from current animal models used in the laboratory; namely rats, mice, guinea pigs, and all others except monkeys, where the secretion of sex steroids takes place exclusively in the gonads (1–3). Primates are thus unique in having adrenals that secrete large amounts of the precursor steroids dehydroepiandrosterone (DHEA) and especially DHEA-sulfate (DHEA-S) that are converted into androstenedione (Δ4-dione) and then into potent androgens and estrogens in peripheral tissues (2, 4).