Luteotrophic agents and steroid substrate utilization.

Abstract

The cells of the CL are derived from precursors in the ovarian follicle. For their existence and function, they are dependent on a combination of various substances, collectively described as luteotrophins. These luteal stimulatory agents, including luteinizing hormone and prolactin from the pituitary, chorionic gonadotrophin from the placenta, and insulin from the pancreas, are classified as endocrine luteotrophins because they are produced at a distance from their target organ, the CL. Paracrine and autocrine luteotrophins are substances produced by the ovary with specific stimulatory effects on the CL: oestrogens and insulin-like growth factors meet this criterion. The CL produces progesterone from cholesterol which can be synthesized de novo or be derived from cholesteryl esters stored in the CL or from free and esterified cholesterol from lipoproteins in circulation. Cholesterol appears to be transported within the luteal cell by means of the cytoskeleton, by a specific, labile intracellular protein and/or by a specific sterol carrier protein. In this review, we have presented evidence to indicate that the luteotrophins have effects on all forms of cholesterol available to the CL. A major mechanism of action of luteotrophins appears to be the management of cholesterol supplies. LH, acting through a cAMP second messenger system, initiates the process of progesterone synthesis by induction of the cleavage of the side-chain on free cholesterol to produce pregnenolone. LH also acts to hydrolyse cholesteryl esters to produce free cholesterol. HDL metabolism appears to be affected by LH, hCG and cAMP. There is good evidence to suggest that luteal cell binding of HDL is regulated, in part, by LH. All phases of the process of utilization of LDL-cholesterol, including the availability of the LDL receptors, internalization of the LDL receptors and ligands into the luteal cell and degradation of LDL, are regulated by LH and cAMP. These agents induce an increase in mRNA for the LDL receptor. These processes may be, in part, controlled by an intracellular negative feedback mechanism for which cholesterol is the effector. However, in experiments where intracellular cholesterol was elevated by hydroxylated cholesterol or by inhibition of the conversion of cholesterol to pregnenolone, it was demonstrated that LH can override the cholesterol negative feedback mechanism. PRL plays an active role in cholesterol homeostasis in the luteal cell. The available evidence suggests that it is not involved in cholesterol side-chain cleavage, and enhances rather than reverses the formation of cholesteryl esters.(ABSTRACT TRUNCATED AT 400 WORDS)