Heterotrimeric C proteins: Organizers of transmembrane signals

The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR).

The mechanism regulating the production of steroids in response to trophic hormone stimulation has been the subject of investigation for over three decades. When considering the effects of trophic hormones on the steroidogenic process it is necessary to first distinguish between acute effects and chronic effects. Acute effects are those which result in the very rapid (within minutes) synthesis and secretion of steroids in response to hormone stimulation and involve the rapid translocation of intracellular cholesterol to the site of its cleavage, as will be discussed later. Chronic effects are those which occur on the order of hours to tens of hours and involve increased gene transcription and translation of the proteins involved in the biosynthesis of steroids. This chapter will focus on studies designed to elucidate the mechanisms involved in the acute regulation of steroid production in response to hormone stimulation. Overviews of the effects of chronic stimulation on steroidogenic enzymes have appeared in several excellent review articles (Simpson and Waterman 1983; Miller 1988; Hanukoglu 1992).

Regulation of the acute production of steroids in steroidogenic cells.

Two types of dopamine receptor whose stimulation affects cellular cyclic AMP have now been identified. In tissues as different as insect ganglia and mammalian neostriatum, stimulation of the dopamine receptor called D-1 increases formation of cyclic AMP1–6, whereas stimulation of the second type of dopamine receptor (D-2)7–11, first identified in the rat pituitary gland, reduces cyclic AMP formation. Recently, a receptor with the pharmacological properties of the D-2 receptor has also been found12–14 in the rat neostriatum; we show here that stimulation of this receptor is followed by a reduction in cyclic AMP formation induced by V stimulation with D-1 agonists.

Opposing roles for D-1 and D-2 dopamine receptors in efflux of cyclic AMP from rat neostriatum.

▪ Abstract Guanine nucleotide binding (G) proteins relay extracellular signals encoded in light, small molecules, peptides, and proteins to activate or inhibit intracellular enzymes and ion channels. The larger G proteins, made up of Gαβγ heterotrimers, dissociate into Gα and Gβγ subunits that separately activate intracellular effector molecules. Only recently has the Gβγ subunit been recognized as a signal transduction molecule in its own right; Gβγ is now known to directly regulate as many different protein targets as the Gα subunit. Recent X-ray crystallography of Gα, Gβγ, and Gαβγ subunits will guide the investigation of structure-function relationships.

G protein beta gamma subunits

Adrenocorticotropin action in isolated adrenal cells. The intermediate role of cyclic AMP in stimulation of corticosterone synthesis.

Actions of choleragen and gonadotropin in isolated Leydig cells. Functional compartmentalization of the hormone-activated cyclic AMP response.

Regulation of steroidogenesis by adrenocorticotropic hormone in isolated adrenal cells. The intermediate role of cyclic nucleotides.

The majority of particulate high-affinity receptors for LH in the steroidogenic cells of the testis and ovary are membrane-bound and capable of functional coupling to adenylate cyclase(1,2) The gonadal receptors for LH can be solubilized together with adenylate cyclase by a variety of non-ionic detergents(3) In addition to the membrane-associated receptors that require detergent for solubilization, the luteinized ovary has been found to contain a small proportion of spontaneously “soluble” receptor sites (up to 10%) that can be recovered in the floating lipid fraction of the 360,000 x g supernate prepared from ovarian homogenates (4)

K Hayashi

Papers

Adrenocorticotropin action in isolated adrenal cells. The intermediate role of cyclic AMP in stimulation of corticosterone synthesis.

Actions of choleragen and gonadotropin in isolated Leydig cells. Functional compartmentalization of the hormone-activated cyclic AMP response.

Regulation of steroidogenesis by adrenocorticotropic hormone in isolated adrenal cells. The intermediate role of cyclic nucleotides.

Gonadal LH Receptors: Resolution from Adenylate Cyclase and Transfer to Heterologous Cells