Development of Responsiveness to Steroid Hormones

Advances in the Biosciences

Alvin M. Kaye, Myra Kaye

• Publisher: Pergamon
• Year: 2013
• Print ISBN:
  9780080249407
• eBook ISBN:
  9781483153087
• Topic: Biological Sciences
• Subtopic: Biology
• Index: Biological Sciences

Development of Responsiveness to Steroid Hormones is a collection of papers presented at the Bat-Sheva Seminar of the same name which was held in Rehovot, Israel, on October 18-26, 1978 and sponsored by the Bat-Sheva de Rothschild Foundation for the Advancement of Science in Israel in cooperation with The Weizmann Institute of Science. Contributors explore how the steroid receptor complex modulates transcription of RNA and cover topics ranging from the sequential acquisition of responsiveness to estrogen in the rat uterus to the ontogeny of steroid receptors in the guinea pig. This book is comprised of 29 chapters and begins with a review of estrogen and estrogen effects in rat uterus and pituitary in culture. The embryonic chick Müllerian duct and several fetal guinea pig organs are then considered, followed by discussions on mammalian and chick liver, multi-hormonal control in rat liver; progesterone and decidualization; and rat mammary gland in culture. Glucocorticoids in developing pancreas, lung, and liver are examined, along with ecdysteroids in both locusts and Drosophila. Refractoriness is exemplified by gonadotropin action in the ovary. The remaining chapters deal with the role of steroid hormone receptors in brain development; the neural trigger for ovulation; aromatization and development of responsiveness of the brain to gonadal steroids; and neuroendocrine correlates of female-offspring interaction in maternal rats. This monograph will be of value to physiologists, biologists, and biochemists.

Sequential Acquisition of Responsiveness to Estrogen in the Rat Uterus

A.M. Kaye, N. Reiss and M.D. Walker, Department of Hormone Research, The Weizmann Institute of Science, Rehovot, Israel

ABSTRACT

The postnatal development of responsiveness to estrogen in the rat uterus can be divided into three stages. In the first stage (lasting for a period of approximately 10 days after birth) a single dose of estrogen, administered to Wistar-derived rats, results in the stimulation of the synthesis of a limited number of uterine proteins. Those which are presently known are the ‘estrogen induced protein’ (IP) first described by Notides and Gorski, ornithine decarboxylase, the first and rate-limiting enzyme in the pathway of polyamine biosynthesis, and estrogen and progesterone receptors. During the second stage of responsiveness, seen at approximately two weeks after birth, both RNA and protein synthesis are stimulated by estrogen, while there is no effect on DNA synthesis. By three weeks after birth, all growth parameters, including DNA synthesis, are increased by estrogen treatment.We have concentrated our investigation on the early and late stages of responsiveness. IP has been characterized and identified as a constitutive component of uterus as well as of pituitary, hypothalamus and cerebral cortex. It has been purified from rat brain where it occurs in both males and females; antisera against it have been made in rabbits and a radioimmunoassay for IP is under development.The stimulation of DNA synthesis by estrogen, as measured by incorporation of tritiated thymidine, was found to be paralleled by an increase in the activity of DNA polymerase α, the putative replicative polymerase, with no increase in DNA polymerase β, possibly a repair enzyme.Throughout the entire period of postnatal development, the presence and, recently, the replenishment, of estrogen receptors have been demonstrated. We therefore use the working hypothesis that the acquisition of responsiveness to estrogen is a result of differentiation of specific chromosomal ‘acceptor sites’ for the estrogenreceptor complex.

Keywords

Estrogen

induced protein

DNA polymerase α

ornithine decarboxylase

receptors

uterus

brain

INTRODUCTION

A steroid hormone such as estrogen, which stimulates the growth and division of uterine cells, displays a wide variety of those actions which culminate in cell division. From both a basic viewpoint-elucidation of the mechanism of regulation of macromolecular synthesis-and an applied approach leading to the safer use of estrogens in contraception and therapy, it is crucial to know whether independent activation of any of estrogen’s actions is experimentally demonstrable. Such a functional dissection of estrogen’s action should provide powerful tools essential for the study of its molecular biology.

Fortunately, for investigation of this problem, the uterus of the rat shows a progressive and differential sensitivity to stimulation by estrogen during the period from birth to puberty. Price and Ortiz (1944) found that when a series of 6 daily injections of estradiol-benzoate (totalling 10 μg) was given to non-inbred rats aged 0 to 50 days, the wet weight increase and estrogen-associated histologic changes in uterus became more pronounced with age up to 26 days after birth. Thereafter the magnitude of these responses declined. A single injection of 0.5 μg estradiol–17β to Sprague-Dawley rats, ovariectomized at 21 days, showed an increase in their uterine weight response until puberty, followed by a decline in responsiveness in older animals (Liu, 1960).

More interestingly, the responsiveness to estrogen can be shown to be acquired in distinct developmental stages when individual components of the overall estrogen response are analyzed (Kaye and colleagues, 1972, 1974, 1975; Katzenellenbogen and Greger, 1974; Sömjen and colleagues, 1973a, b, 1974; Walker and colleagues, 1976, 1978; Peleg and colleagues, 1977, 1979; Peleg and Kaye, 1978). In perinatal life, although estrogen receptors are present in uterine cytoplasm and are capable of being transferred into the nucleus, there is a period of approximately two weeks after birth during which there is a stimulation of synthesis of a limited number of proteins following a single estrogen injection. Bulk protein and RNA synthesis can be stimulated by estrogen only after, the second week of life. DNA synthesis is accelerated by estrogen only in uteri of rats that are 20 days of age or older.

The emphasis in this review will be placed on the initial stage of the acquisition of estrogen responsiveness epitomized by the ‘estrogen induced protein’ first described by Notides and Gorski (1966) and on the culminating stage of stimulation of DNA synthesis.

THE PERINATAL STAGE OF RESPONSIVENESS: STIMULATION OF A SMALL GROUP OF PROTEINS

Steroid Receptors

Estrogen receptors have been demonstrated in rat fetal Mullerian duct (the precursor of the uterus) in fetuses one day before birth (Sömjen and colleagues, 1976). In order to detect the characteristic 8S receptor in the presence of the overwhelming fetal concentration of α-fetoprotein (see Nunez and colleagues, 1979; Raynaud and colleagues, 1979), which sediments at 4S, ³H-diethylstilbestrol was used as ligand instead of ³H-estradiol–17β. This synthetic estrogen was used (Fig. 1) because it shows only one thirteenth of the binding of ³H-estradiol to α-fetoproteinrich blood plasma from 11 day old rats. The developmental implication of circulating α-fetoprotein in newborn rats have been reviewed recently (c, f, Kaye, 1978; Raynaud and colleagues, 1979).

Fig. 1 Sedimentation analysis of cytoplasmic estrogen binding proteins from the Müllerian duct and kidney of 20-day-old rat fetuses. Cytosol preparations from (a) the Müllerian duct (Δ——Δ) and (b) the kidney (

——

) of 8 rat fetuses taken on the 20th day of gestation were incubated in 1 nM (³H)diethylstilbestrol for 2 h at 0°C and ...

Table of contents

• Cover image
• Title page
• Table of Contents
• Inside Front Cover
• Copyright
• Preface
• Chapter 1: Sequential Acquisition of Responsiveness to Estrogen in the Rat Uterus
• Chapter 2: Regulation of Prolactin Synthesis by Estrogen
• Chapter 3: Rodent Alpha1-Fetoprotein and its Interaction with Estrogens
• Chapter 4: Influence of Rat Estradiol Binding Plasma Protein (EBP) on Estrogen Binding to its Receptor and on Induced Biological Responses
• Chapter 5: Ontogeny of the Receptor and Responsiveness to Estrogen in the Genital Tract of the Chick Embryo
• Chapter 6: Ontogeny of Steroid Receptors in the Guinea Pig
• Chapter 7: Estrogen Receptor in the Mammalian Liver: Developmental and Metabolic Aspects
• Chapter 8: The Development of Estrogen Receptors and of the Vitellogenic Response to Estradiol in Embryonic Chick Liver
• Chapter 9: Development of Hormonal Control of Histidase
• Chapter 10: Functional Development of Rat Trophoblast and Decidual Cells During Establishment of the Hemochorial Placenta
• Chapter 11: The Role of Progesterone in Induction of Decidualization in the Uterus of the Pseudopregnant Rat
• Chapter 12: Modulation of Progesterone Metabolizing Enzyme in Lymphocytes During Development and by Endocrine Manipulation
• Chapter 13: Alterations in Steroid-Responsiveness During Ontogeny of Mouse Mammary Epithelium
• Chapter 14: Differential Response of Embryonic Chick Pancreas Enzymes to Glucocorticoids
• Chapter 15: Glucocorticoids and Fetal Lung Development
• Chapter 16: Developmental Changes in the Glucocorticoid Induction of Hepatic Tyrosine Aminotransferase
• Chapter 17: Sequential Action of Ecdysone and 20-Hydroxyecdysone on Locust Epidermis
• Chapter 18: Ecdysteroid Action in Imaginai Discs of Drosophila Melanogaster
• Chapter 19: Control by Estrogen of Reversible Gene Expression: The Vitellogenin Model
• Chapter 20: Development of Refractoriness of the Ovarian Cyclic AMP System to Gonadotrophins
• Chapter 21: Control of Responsiveness to Gonadotropins and Steroids in the Neonatal Rat Ovary
• Chapter 22: Development of Ovarian Responsiveness: Follicle Maturation and Luteinization
• Chapter 23: Receptors for Glucocorticosteroids in the Embryonic Neural Retina in Relation to the Development of the Biological Response
• Chapter 24: Steroid Hormone Receptors During Brain Development
• Chapter 25: The Neural Trigger for Ovulation - A Safety Catch
• Chapter 26: Aromatization and Development of Responsiveness of the Brain to Gonadal Steroids
• Chapter 27: Sex Differentiation of Cyclic Gonadotropin Secretion
• Chapter 28: Sex-Specific Orientation in Female and Male Rats: Development and Effects of Early Endocrine Manipulation
• Chapter 29: Neuroendocrine Correlates of Female-Offspring Interaction in Maternal Rats
• Participants
• Subject Index