The primary function of the corpus luteum is secretion of the hormone progesterone, which is required for maintenance of normal pregnancy in mammals. The corpus luteum develops from residual follicular granulosal and thecal cells after ovulation. Luteinizing hormone (LH) from the anterior pituitary is important for normal development and function of the corpus luteum in most mammals, although growth hormone, prolactin, and estradiol also play a role in several species. The mature corpus luteum is composed of at least two steroidogenic cell types based on morphological and biochemical criteria and on the follicular source of origin. Small luteal cells appear to be of thecal cell origin and respond to LH with increased secretion of progesterone. LH directly stimulates the secretion of progesterone from small luteal cells via activation of the protein kinase A second messenger pathway. Large luteal cells are of granulosal cell origin and contain receptors for PGF(2alpha) and appear to mediate the luteolytic actions of this hormone. If pregnancy does not occur, the corpus luteum must regress to allow follicular growth and ovulation and the reproductive cycle begins again. Luteal regression is initiated by PGF(2alpha) of uterine origin in most subprimate species. The role played by PGF(2alpha) in primates remains controversial. In primates, if PGF(2alpha) plays a role in luteolysis, it appears to be of ovarian origin. The antisteroidogenic effects of PGF(2alpha) appear to be mediated by the protein kinase C second messenger pathway, whereas loss of luteal cells appears to follow an influx of calcium, activation of endonucleases, and an apoptotic form of cell death. If the female becomes pregnant, continued secretion of progesterone from the corpus luteum is required to provide an appropriate uterine environment for maintenance of pregnancy. The mechanisms whereby the pregnant uterus signals the corpus luteum that a conceptus is present varies from secretion of a chorionic gonadotropin (primates and equids), to secretion of an antiluteolytic factor (domestic ruminants), and to a neuroendocrine reflex arc that modifies the secretory patterns of hormones from the anterior pituitary (most rodents).
Interferon tau (IFNT) from the ovine conceptus has paracrine actions on the endometrium that alter release of prostaglandin F(2alpha) (PGF) and protect the corpus luteum (CL). Antiviral activity in uterine vein blood and expression of interferon-stimulated genes (ISGs) in CL is greater in pregnant than in nonpregnant ewes. We hypothesized that IFNT contributes to antiviral activity in uterine vein blood and has endocrine actions on the CL. Preadsorption of IFNT with antiserum against recombinant ovine (ro) IFNT revealed that antiviral activity in uterine vein blood from pregnant ewes was mediated by IFNT. Endocrine actions of IFNT were examined after infusing either roIFNT or bovine serum albumin (BSA; 200 microg/24 h; mini-osmotic pump) into the uterine vein of nonpregnant ewes from Day 10 to Day 11 postestrus. The abundance of ISG15 mRNA and protein was greater in CL (P < 0.05) from ewes receiving 24-h roIFNT infusion compared to that from ewes receiving 24-h BSA infusion. Injection of PGF at 12 h following insertion of mini-osmotic pumps resulted in a decline in serum progesterone concentrations 6 through 12 h later in BSA-infused ewes; however, in roIFNT-infused ewes, a similar decline in progesterone concentrations at 6 h was followed by recovery to control values at 12 h. Ewes then received infusions (200 microg/day) of either roIFNT or BSA for 7 days beginning on Day 10 of the estrous cycle. All BSA-infused ewes returned to estrus by Day 19, whereas 80% of roIFNT-infused ewes maintained luteal-phase concentrations of progesterone through Day 32. In conclusion, IFNT is released from the uterus into the uterine vein and acts through an endocrine mechanism to induce ISGs in the CL and delay luteolysis.
The control of progesterone synthesis in the corpus luteum is more complex than is shown in the general pathway for biosynthesis of progesterone in a luteal cell ( Fig. 1) because there are at least two morphologically and biochemically distinct steroidogenic types of cell in the corpus luteum of cattle and sheep and most other mammalian species (Niswender and Nett, 1994; Fig. 2). In ewes, small luteal cells are 12-20 µm in diameter, thought to be of follicular thecal cell origin, contain receptors for LH, respond to LH or cAMP with a 5-15-fold increase in secretion of progesterone, and often contain numerous lipid droplets. Large luteal cells (> 20 µm) are primarily of granulosal cell origin, secrete high basal concentrations of progesterone, and although LH receptors are present, do not respond to LH or cAMP with increased secretion of progesterone. Large cells contain receptors for PGF 2α and respond to this hormone with activation of at least two second messenger pathways. Activation of protein kinase C (PKC) results in decreased secretion of progesterone. Increased concentrations of intracellular free calcium (Wiltbank et al., 1991) resulting from increased binding of PGF 2α to its receptor appear to induce apoptosis and cell death. Steroidogenic luteal cells also contain a broad array of receptors for additional regulatory hormones and factors that may or may not be cell-type specific.
Chronic regulation of the secretion of progesteroneIt has been known for some time that LH is critical for normal luteal function in domestic animals (Kaltenbach et al., 1968; Denamur et al., 1973; Hansel et al., 1973). Many of the actions of LH on luteal cells have been elucidated and both acute and long-term effects of LH on luteal steroidogenesis have been demonstrated. Stimulation by LH is critical for the long-term steroidogenic capability of luteal cells, including maintenance of normal amounts of mRNA encoding 3β-hydroxysteroid dehydrogenase/∆ 5 ,∆ 4 isomerase (3β-HSD), cytochrome P450 side chain cleavage enzyme
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