Influence of rat estradiol binding plasma protein (EBP) on uterotrophic activity

doi:10.1016/S0039-128X(73)80009-1

Steroids

Volume 21, Issue 2, February 1973, Pages 249-258

https://doi.org/10.1016/S0039-128X(73)80009-1 Get rights and content

Abstract

The specificity of estradiol binding to EBP and the decrease in the number of specific binding sites with age have been used to show that a plasma protein may modulate a tissue response by controlling the free steroid concentration.

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Cited by (144)

Kisspeptin neurons as a key player bridging the endocrine system and sexual behavior in mammals
2022, Frontiers in Neuroendocrinology
Citation Excerpt :
On the other hand, in female rodents, the neural circuit of lordosis behavior develops in a steroid-independent manner. It should be noted that the female rodent brain is also sensitive to sex steroids in the “critical period” (Whalen & Nadler 1963; Södersten 1973), but the brain is largely protected by α-fetoprotein, a plasma protein produced by fetal endodermal cells, that traps the estrogen derived from the perinatal ovaries and/or mother (Raynaud 1973; McEwen et al. 1975; Bakker et al. 2006). On the other hand, the “activational effect” of steroid hormones on controlling sexual behavior is defined as a reversible and transient effect of testicular testosterone and ovarian estradiol on the occurrence of male-type and female-type sexual behavior in male and female rodents, respectively, in adulthood (Blaustein 2008; Hull & Dominguez 2019).
Reproductive behaviors are sexually differentiated: for example, male rodents show mounting behavior, while females in estrus show lordosis behavior as sex-specific sexual behaviors. Kisspeptin neurons govern reproductive function via direct stimulation of gonadotropin-releasing hormone (GnRH) and subsequent gonadotropin release for gonadal steroidogenesis in mammals. First, we discuss the role of hypothalamic kisspeptin neurons as an indispensable regulator of sexual behavior by stimulating the synthesis of gonadal steroids, which exert “activational effects” on the behavior in adulthood. Second, we discuss the central role of kisspeptin neurons that are directly involved in neural circuits controlling sexual behavior in adulthood. We then focused on the role of perinatal hypothalamic kisspeptin neurons in the induction of perinatal testosterone secretion for its “organizational effects” on masculinization/defeminization of the male brain in rodents during a critical period. We subsequently concluded that kisspeptin neurons are key players in bridging the endocrine system and sexual behavior in mammals.
Alpha-fetoprotein in animal reproduction
2019, Research in Veterinary Science
Citation Excerpt :
In physiological conditions, the new-borns of all species, present high AFP levels at birth, after which they decrease by about 50% during the first 24 h. In rats, only trace levels of AFP (about 0.01% of foetal levels) are detected at 3 weeks of age (Raynaud, 1973). Human normal adult levels typically range between 1 and 40 ng/ml (Mizejewski, 2002), whereas in pregnant women, the AFP concentrations are much higher.
Alpha-fetoprotein (AFP) is a serum glycoprotein with structural and physico-chemical properties similar to albumin. However, the exact physiological functions of AFP remain unknown; those known to date include markers to pathological conditions including neoplastic and non-neoplastic diseases, antioxidant effects, growth regulator in different cells and in cancer, immune response modulator, and carrier for fatty acids and oestrogens. This review aimed to present an overview of the different functions of AFP, particularly its role in the sexual differentiation of the hypothalamus, because its ability to bind oestrogens prevents their passage to the brain, where they inhibit the surge centre development. AFP and anti-Mullerian hormone are known to be involved in the development of freemartins, or genetically female foetuses masculinised in the presence of a male co-twin.
Hormones of choice: The neuroendocrinology of partner preference in animals
2011, Frontiers in Neuroendocrinology
Partner preference behavior can be viewed as the outcome of a set of hierarchical choices made by an individual in anticipation of mating. The first choice involves approaching a conspecific verses an individual of another species. As a rule, a conspecific is picked as a mating partner, but early life experiences can alter that outcome. Within a species, an animal then has the choice between a member of the same sex or the opposite sex. The final choice is for a specific individual. This review will focus on the middle choice, the decision to mate with either a male or a female. Available data from rats, mice, and ferrets point to the importance of perinatal exposure to steroid hormones in the development of partner preferences, as well as the importance of activational effects in adulthood. However, the particular effects of this hormone exposure show species differences in both the specific steroid hormone responsible for the organization of behavior and the developmental period when it has its effect. Where these hormones have an effect in the brain is mostly unknown, but regions involved in olfaction and sexual behavior, as well as sexually dimorphic regions, seem to play a role. One limitation of the literature base is that many mate or ‘partner preference studies’ rely on preference for a specific stimulus (usually olfaction) but do not include an analysis of the relation, if any, that stimulus has to the choice of a particular sexual partner. A second limitation has been the almost total lack of attention to the type of behavior that is shown by the choosing animal once a ‘partner’ has been chosen, specifically, if the individual plays a mating role typical of its own sex or the opposite sex. Additional paradigms that address these questions are needed for better understanding of partner preferences in rodents.
Estrogen action: A historic perspective on the implications of considering alternative approaches
2010, Physiology and Behavior
Citation Excerpt :
AFP is 69 kD glycoprotein secreted primarily by the fetal liver [32–34]. Its presence in appreciable levels in the circulation of adults is limited to the maternal bloodstream, during pregnancy until parturition [32,35,36], and, to a lesser extent, production by some tumors. Over two decades ago, it was hypothesized that exposure levels of AFP underlie reduced risk of breast cancer in women [37], and that this was due to endocrine action of this protein on premalignant tissues that would have developed cancer many years after pregnancy [38].
In the 50 years since the initial reports of a cognate estrogen receptor (ER), much has been learned about the diverse effects and mechanisms of estrogens, such as 17β-estradiol (E₂). This expert narrative review briefly summarizes perspectives and/or recent work of the authors, who have been addressing different aspects of estrogen action, but take a common approach of using alternative considerations to gain insight into mechanisms with clinical relevance, and inform future studies, regarding estrogen action. Their “Top Ten” favorite alternatives that are discussed herein are as follows. 1 — E₂ has actions by binding to a receptor that do not require its enzymatic conversion. 2 — Using a different strategy for antibody binding could make the estrogen receptor (ER) more discernible. 3 — Blocking ERs, rather than E₂ production, may be a useful strategy for breast cancer therapy. 4 — Secretion of α-fetoprotein (AFP), rather than only levels of E₂ and/or progesterone, may influence breast cancer risk. 5 — A peptide derived from the active site of AFP can produce the same benefits of the entire endogenous protein in endocrine cancers. 6 — Differential distribution of ER subtypes in the body and brain may underlie specific effects of estrogens. 7 — ERβ may be sufficient for the trophic effects of estrogen in the brain, and ERα may be the primary target of trophic effects in the body. 8 — ERβ may play a role in the trophic effects of androgens, and may also be relevant in the periphery. 9 — Downstream of E₂'s effects at ERβ, there may be consequences for biosynthesis of progestogens and/or androgens. 10 — Changes in histones and/or other factors, which may be downstream of ERβ, potentially underlie the divergent effects of E₂ in the brain and peripheral tissues.
Prepubertal estrogen exposure modifies neurotrophin receptor expression in celiac neurons and alters ovarian innervation
2009, Autonomic Neuroscience: Basic and Clinical
Estradiol is a key hormone in the regulation of reproductive processes acting both on peripheral organs and sympathetic neurons associated to reproductive function. However, many of its regulatory effects on the development and function on the sympathetic neurons have not been completely clarified. Sympathetic neurons located in the celiac ganglion projects to visceral, vascular and glandular targets, and contribute to ovarian innervation, being the main source of sympathetic fibers. In the present study, we analyze the effects of elevated levels of exogenous estrogen during the prepubertal period in post-ganglionic sympathetic neurons. Estrogen exposure induced a significant increase in sympathetic celiac neuronal size and modified the expression of neurotrophin receptor p75. This change affected mainly small and medium size neurons. The effect of estrogens on innervation of celiac target organs was heterogeneous, inducing a significant increase in catecholaminergic innervation of the ovary, but not of the pyloric muscular layers. These findings further support the role of estrogen as a modulator of neuronal plasticity and suggest that estrogen could modify some features involved in the relation between sympathetic immature peripheral neurons and their target organs throughout a neurotrophin-dependent mechanism.
Role for estradiol in female-typical brain and behavioral sexual differentiation
2008, Frontiers in Neuroendocrinology
Citation Excerpt :
However, we now know that any prenatal estrogen action is blocked by AFP in the developing female, thus if estrogens normally contributes to the development of the female brain, they most likely act postnatally when the amount of AFP has decreased substantially and AFP no longer plays a protective role. AFP levels are the highest at birth, after which they decrease by about 50% during the first 24 h. Only trace levels (about 0.01% of fetal levels) are detected at 3 weeks of age in rats [83]. Thus presumably when the ovaries start to secrete estrogens at day 7 after birth [53], AFP no longer plays a significant role.
The importance of estrogens in controlling brain and behavioral sexual differentiation in female rodents is an unresolved issue in the field of behavioral neuroendocrinology. Whereas, the current dogma states that the female brain develops independently of estradiol, many studies have hinted at possible roles of estrogen in female sexual differentiation. Accordingly, it has been proposed that α-fetoprotein, a fetal plasma protein that binds estrogens with high affinity, has more than a neuroprotective role and specifically delivers estrogens to target brain cells to ensure female differentiation. Here, we review new results obtained in aromatase and α-fetoprotein knockout mice showing that estrogens can have both feminizing and defeminizing effects on the developing neural mechanisms that control sexual behavior. We propose that the defeminizing action of estradiol normally occurs prenatally in males and is avoided in fetal females because of the protective actions of α-fetoprotein, whereas the feminizing action of estradiol normally occurs postnatally in genetic females.

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Influence of rat estradiol binding plasma protein (EBP) on uterotrophic activity

Abstract

Steroids

Biochem. Biophys. Res. Communications

J. Biol. Chem.

Endocrinology

C.R. Acad. Sc. Paris