Marc E. Freeman

Bio: Marc E. Freeman is an academic researcher from Florida State University. The author has contributed to research in topics: Prolactin & Prolactin cell. The author has an hindex of 35, co-authored 93 publications receiving 5392 citations.

Prolactin: Structure, Function, and Regulation of Secretion

Abstract: Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of posttranslational forms ranging from size variants to chemical modifications such as phosphorylation or glycosylation. It is not only synthesized in the pituitary gland, as originally described, but also within the central nervous system, the immune system, the uterus and its associated tissues of conception, and even the mammary gland itself. Moreover, its biological actions are not limited solely to reproduction because it has been shown to control a variety of behaviors and even play a role in homeostasis. Prolactin-releasing stimuli not only include the nursing stimulus, but light, audition, olfaction, and stress can serve a stimulatory role. Finally, although it is well known that dopamine of hypothalamic origin provides inhibitory control over the secretion of prolactin, other factors within the brain, pituitary gland, and peripheral organs have been shown to inhibit or stimulate prolactin secretion as well. It is the purpose of this review to provide a comprehensive survey of our current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.

CHAPTER 43 – Neuroendocrine Control of the Ovarian Cycle of the Rat

Abstract: This chapter discusses the control of the ovarian cycle of the rats by the brain and its interaction with the anterior pituitary gland and ovaries. The ovarian cycle of the rats is characterized by a brief luteal phase, and the events of the cycle are largely under photoperiodic control. That is, the lighting periodicity plays a dominant role in the incidence and duration of the stages of the ovarian cycle. During the estrous cycle of the rat, three or more generations of corpora lutea can be present on the ovary from the immediately preceding ovulatory cycles whereas the preovulatory period of the estrous cycle is characterized by a growth of ovarian follicles and a concomitant enhanced secretion of estrogen. The secretion rate of estradiol into ovarian venous plasma is low on estrus, begins to rise significantly by late on metestrus through the morning of diestrus, and reaches peak concentrations by the afternoon of proestrus.

The mating-induced release of prolactin: a unique neuroendocrine response.

Abstract: I. Introduction IN THE RAT, the corpus luteum is formed on the morning of estrus in response to the surge of luteinizing hormone released on the previous day, proestrus. However, unlike other mammals whose corpora lutea secrete increasing amounts of progesterone for several days (1), the newly formed corpora lutea of the rat secrete progesterone for only 2 days after formation (2, 3). In the absence of all other input, the corpora lutea subsequently fail and progesterone secretion wanes (3). It has long been appreciated that rodent corpora lutea could be maintained by either coital stimulation (4) or injection of pituitary extracts containing prolactin (PRL) activity (5, 6). An overwhelming literature now indicates that the mating stimulus induces the release of PRL which in turn “rescues” the corpora lutea of the cycle and prolongs the ability of these structures to secrete progesterone (3, 7–11). The mating stimulus or copulomimetic stimuli applied to the uterine cervix with a glass rod or appropriately...

Ovarian Steroid Modulation of Prolactin Surges in Cervically Stimulated Ovariectomized Rats

Abstract: PRL secretion induced by cervical stimulation (CS) in the intact rat is characterized by a daily diurnal surge (1900 h) which recurs for 10 days and a daily nocturnal surge (0500 h) which lasts for 11 days. In ovariectomized (OV) rats, CS induces attenuated PRL surges which last for only 6 days. This study describes the effect of SC Silastic implants of estradiol (E2) or progesterone (P) on the magnitude and persistence of PRL surges in OV-CS rats. Placement of P at 1500 h and CS at 1900 h day 0 (D-0) resulted in nocturnal surges of PRL on D-2 which were significantly greater than those of blank-implanted rats. Diurnal surges of PRL on D-2 were equivalent in P and blank-implanted rats. Placement of E2 at 0800 h on the day before CS at 1900 h on D-0 resulted in an enhanced diurnal surge and extinction of the nocturnal surge of PRL on D-2 compared to blank-implanted rats. In the absence of CS, OV rats presented diurnal but no nocturnal surges of PRL in response to E2. When steroid implantation was delayed u...

The use of the elevated plus maze as an assay of anxiety-related behavior in rodents

Abstract: The elevated plus maze is a widely used behavioral assay for rodents and it has been validated to assess the anti-anxiety effects of pharmacological agents and steroid hormones, and to define brain regions and mechanisms underlying anxiety-related behavior. Briefly, rats or mice are placed at the junction of the four arms of the maze, facing an open arm, and entries/duration in each arm are recorded by a video-tracking system and observer simultaneously for 5 min. Other ethological parameters (i.e., rears, head dips and stretched-attend postures) can also be observed. An increase in open arm activity (duration and/or entries) reflects anti-anxiety behavior. In our laboratory, rats or mice are exposed to the plus maze on one occasion; thus, results can be obtained in 5 min per rodent.

Prolactin: Structure, Function, and Regulation of Secretion

Abstract: Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of posttranslational forms ranging from size variants to chemical modifications such as phosphorylation or glycosylation. It is not only synthesized in the pituitary gland, as originally described, but also within the central nervous system, the immune system, the uterus and its associated tissues of conception, and even the mammary gland itself. Moreover, its biological actions are not limited solely to reproduction because it has been shown to control a variety of behaviors and even play a role in homeostasis. Prolactin-releasing stimuli not only include the nursing stimulus, but light, audition, olfaction, and stress can serve a stimulatory role. Finally, although it is well known that dopamine of hypothalamic origin provides inhibitory control over the secretion of prolactin, other factors within the brain, pituitary gland, and peripheral organs have been shown to inhibit or stimulate prolactin secretion as well. It is the purpose of this review to provide a comprehensive survey of our current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.

Prolactin (PRL) and Its Receptor: Actions, Signal Transduction Pathways and Phenotypes Observed in PRL Receptor Knockout Mice

Abstract: PRL is an anterior pituitary hormone that, along with GH and PLs, forms a family of hormones that probably resulted from the duplication of an ancestral gene. The PRLR is also a member of a larger family, known as the cytokine class-1 receptor superfamily, which currently has more than 20 different members. PRLRs or binding sites are widely distributed throughout the body. In fact, it is difficult to find a tissue that does not express any PRLR mRNA or protein. In agreement with this wide distribution of receptors is the fact that now more than 300 separate actions of PRL have been reported in various vertebrates, including effects on water and salt balance, growth and development, endocrinology and metabolism, brain and behavior, reproduction, and immune regulation and protection. Clearly, a large proportion of these actions are directly or indirectly associated with the process of reproduction, including many behavioral effects. PRL is also becoming well known as an important regulator of immune function. A number of disease states, including the growth of different forms of cancer as well as various autoimmune diseases, appear to be related to an overproduction of PRL, which may act in an endocrine, autocrine, or paracrine manner, or via an increased sensitivity to the hormone. The first step in the mechanism of action of PRL is the binding to a cell surface receptor. The ligand binds in a two-step process in which site 1 on PRL binds to one receptor molecule, after which a second receptor molecule binds to site 2 on the hormone, forming a homodimer consisting of one molecule of PRL and two molecules of receptor. The PRLR contains no intrinsic tyrosine kinase cytoplasmic domain but associates with a cytoplasmic tyrosine kinase, JAK2. Dimerization of the receptor induces tyrosine phosphorylation and activation of the JAK kinase followed by phosphorylation of the receptor. Other receptor-associated kinases of the Src family have also been shown to be activated by PRL. One major pathway of signaling involves phosphorylation of cytoplasmic State proteins, which themselves dimerize and translocate to nucleus and bind to specific promoter elements on PRL-responsive genes. In addition, the Ras/Raf/MAP kinase pathway is also activated by PRL and may be involved in the proliferative effects of the hormone. Finally, a number of other potential mediators have been identified, including IRS-1, PI-3 kinase, SHP-2, PLC gamma, PKC, and intracellular Ca2+. The technique of gene targeting in mice has been used to develop the first experimental model in which the effect of the complete absence of any lactogen or PRL-mediated effects can be studied. Heterozygous (+/-) females show almost complete failure to lactate after the first, but not subsequent, pregnancies. Homozygous (-/-) females are infertile due to multiple reproductive abnormalities, including ovulation of premeiotic oocytes, reduced fertilization of oocytes, reduced preimplantation oocyte development, lack of embryo implantation, and the absence of pseudopregnancy. Twenty per cent of the homozygous males showed delayed fertility. Other phenotypes, including effects on the immune system and bone, are currently being examined. It is clear that there are multiple actions associated with PRL. It will be important to correlate known effects with local production of PRL to differentiate classic endocrine from autocrine/paracrine effects. The fact that extrapituitary PRL can, under some circumstances, compensate for pituitary PRL raises the interesting possibility that there may be effects of PRL other than those originally observed in hypophysectomized rats. The PRLR knockout mouse model should be an interesting system by which to look for effects activated only by PRL or other lactogenic hormones. On the other hand, many of the effects reported in this review may be shared with other hormones, cytokines, or growth factors and thus will be more difficult to study. (ABSTRACT TRUNCATED)

Mammalian G proteins and their cell type specific functions

Abstract: Heterotrimeric G proteins are key players in transmembrane signaling by coupling a huge variety of receptors to channel proteins, enzymes, and other effector molecules. Multiple subforms of G proteins together with receptors, effectors, and various regulatory proteins represent the components of a highly versatile signal transduction system. G protein-mediated signaling is employed by virtually all cells in the mammalian organism and is centrally involved in diverse physiological functions such as perception of sensory information, modulation of synaptic transmission, hormone release and actions, regulation of cell contraction and migration, or cell growth and differentiation. In this review, some of the functions of heterotrimeric G proteins in defined cells and tissues are described.