Luteal regression: a redefinition of the terms
© Bowen-Shauver and Telleria; licensee BioMed Central Ltd. 2003
Received: 13 February 2003
Accepted: 24 March 2003
Published: 24 March 2003
The corpus luteum is a transient endocrine gland that is specialized for the production of progesterone and that plays a critical role in the establishment and maintenance of pregnancy. The life span of the corpus luteum varies between species and, within a species, can be dramatically altered by events such as mating or pregnancy. Regardless of the duration of its life span, the corpus luteum eventually enters a dynamic regression process during which it loses the capacity to produce progesterone and undergoes structural involution.
Results of a cursory MEDLINE/PubMed search performed on November 2002 using the terms as listed.
Total Number of Articles Retrieved
Number of Articles Retrieved for Period 2001–2002
"functional luteal regression"
"structural luteal regression"
To quote Rossdale and Cox in their communication entitled Terminology: a mark of scientific progress : "Scientific terminology must be as exact as is possible within the state of knowledge available." As our knowledge of the molecular mechanisms participating in the process of luteal regression evolves, some of the commonly used terms cited above have been rendered obsolete, inappropriate, and even incorrect. The foremost of these is "luteolysis," still one of the most common terms used to define the process of luteal regression, most probably because it is listed among Medical Subject Headings (MeSH), and, therefore, used most frequently. MeSH is the U.S. National Library of Medicine's controlled vocabulary used for indexing articles in PubMed. MeSH terminology provides a consistent way to retrieve information that may use different terminology for the same concepts. In MeSH, "luteolysis" is defined as "degradation of corpus luteum" and further described as "...characterized by the involution and cessation of its endocrine function." From a cell biology point of view, "lysis" means "rupture of cell plasma membrane, leading to the release of cytoplasm and the death of the cell" . If interpreted with strict accordance to the Latin, lysis refers to "disintegration," as recently discussed by Davis and Rueda . Over the last decade, it has become clear that the involution of the corpus luteum is associated with a phenomenon of programmed cell death or apoptosis . Because apoptosis is an organized process that does not involve a major inflammatory response, and because the majority of cells are removed prior to rupture, the term "lysis" when applied to luteal regression is largely inaccurate. Therefore, while the term luteolysis remains very popular – 1251 manuscripts were retrieved using the word "luteolysis" and only 403 were retrieved using the terms "luteal regression" in the MEDLINE/PubMed search (see Table 1) – this term no longer accurately reflects the mechanisms involved in luteal regression. In 1999, McCraken et al.  stated that "the term luteolysis may be something of a misnomer;" but also referred to the deep entrenchment of this term in the literature. However, the exponential increase in the number of scientific manuscripts published in recent years ensures that a prompt move to replace the older term with a more accurate descriptor will rapidly result in an overturn of the current ranking displayed in Table 1 and that only a minority of papers will continue to be retrieved using the older term.
Despite the fact that a strict definition of "luteolysis" appears to regard only the structural disintegration of the corpus luteum, broader interpretations are rife within the literature. Rothchild  defined luteolysis as "stopping the secretion of progesterone by the corpus luteum." Two other recent reviews take a middle road. Hoyer  refers to the fall in progesterone secretion as functional regression but considers structural regression, or cell death, the "true" regression. Niswender et al. , while referring to luteal regression as the structural demise of the corpus luteum, go on to describe the loss of progesterone synthesis and secretion – not a structural event – as part of the regression of the corpus luteum.
As the previous paragraph shows, the adjectives "structural" and "functional" cannot be overlooked when addressing terminology in the field of luteal regression. These words have had a consistent presence in literature concerning the regression of the corpus luteum since Malven and Sawyer  described the process of luteal regression in the rat as having two components: "1) an initial termination of luteal secretory function and 2) a subsequent morphological regression of the nonfunctioning corpora lutea." A few years later Malven et al.  used the term "structural luteolysis" to describe the morphological regression of persistent, nonfunctional corpora lutea in the hypophysectomized rat. The definition of "nonfunctional" provided in this manuscript expanded upon the 1966 description of the first component of luteal regression in the rat by explaining that the corpora lutea "did not secrete enough progesterone to induce deciduoma formation following endometrial traumatization." Thus, the corpora lutea were "nonfunctional" in terms of progesterone production and the potential for establishment of pregnancy.
Since the appearance of these early papers, the terms functional and structural regression of the corpus luteum (or the more popular phrasing "functional and structural luteolysis") have gained relative acceptance and usage. The cursory MEDLINE/PubMed search shown in Table 1 turned up 82 references containing the phrase "functional luteolysis," of which 5 were 2001 and 2002 publications, and 72 references containing the phrase "structural luteolysis," of which 14 were 2001 and 2002 publications. The prevalence of the term "structural luteolysis" over "functional luteolysis" in recently published articles may be due in part to a greater disparity in the perceived meaning of the latter term. This stems largely from studies in rats, in which it was revealed that corpora lutea which no longer secreted significant quantities of progesterone retained many functions, including active steroidogenesis [11–13].
It is our contention that these two frequently described components of the process of luteal regression (i.e. cessation of progesterone secretion and disappearance of the structure) merit equal attention. However, the timing and inter-relationship of these two types of regressive changes appears to vary by species. As new information on the molecular steps triggered during luteal regression is obtained, these mechanisms will need to be defined as they relate to these facets of the overall regressive process. Davis and Rueda  advised that the terms functional and structural used in the context of luteal regression should be adequately defined by the authors in the context of the particular species and reproductive stage being studied, with which we concur. It is not extreme to predict that with the advancement of knowledge in the process of luteal regression researchers will find increasing difficulties in establishing the limits as to what mechanisms belong to the "functional" facet of luteal regression, and which ones are part of the "structural" facet, as luteal regression is a process of synchronized events. For example, it now appears that progesterone itself is responsible for preventing the onset of apoptosis and structural disintegration [14–17].
These authors strongly recommend that the term luteal regression should be used to refer to the process of regression of the corpus luteum. Luteal regression represents a broad definition of the process of demise of the corpus luteum that is capable of accommodating all new knowledge evolved on the molecular mechanisms activated or inhibited during the process of regression of the corpus luteum regardless of species or reproductive stage. Further, according to the etymology of the word, luteolysis has a very limited meaning that no longer describes properly the complex sequence of synchronized molecular events associated with the demise of the corpus luteum. The modifying terms "functional" and "structural" can be used in conjunction with the term luteal regression to further identify aspects of the overall process but must be adequately defined within the context of the publication.
- Rossdale PD, Cox JE: Terminology: a mark of scientific progress. Equine Veterinary Journal. 1990, 22: 150-View ArticlePubMedGoogle Scholar
- Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P: Biology of the Cell. New York: Garland Science, Taylor and Francis Group. 2002, G: 21-Google Scholar
- Davis JS, Rueda BR: The corpus luteum: an ovarian structure with maternal instincts and suicidal tendencies. Frontiers in Bioscience. 2002, 7: d1949-d1978.View ArticlePubMedGoogle Scholar
- Tilly JL: The molecular basis of ovarian cell death during germ attrition, follicular atresia, and luteolysis. Frontiers in Bioscience. 1996, 1: d1-d11.PubMedGoogle Scholar
- McCraken JA, Custer ED, Lamsa JC: Luteolysis: a neuroendocrine-mediated event. Physiological Reviews. 1999, 79: 263-324.Google Scholar
- Rothchild I: The regulation of the mammalian corpus luteum. Recent Progress in Hormone Research. 1981, 37: 183-298.PubMedGoogle Scholar
- Hoyer PB: Regulation of luteal regression: the ewe as a model. Journal of the Society for Gynecologic Investigation. 1998, 5: 49-57. 10.1016/S1071-5576(97)00105-6.View ArticlePubMedGoogle Scholar
- Niswender GD, Juenguel JL, Silva RJ, Rollyson MK, McIntush EW: Mechanisms controlling the function and life span of the corpus luteum. Physiological Reviews. 2000, 80: 1-29.PubMedGoogle Scholar
- Malven PV, Sawyer CH: A luteolytic action of prolactin in hypophysectomized rats. Endocrinology. 1966, 79: 268-274.View ArticlePubMedGoogle Scholar
- Malven PV, Cousar GJ, Row EH: Structural luteolysis in hypophysectomized rats. American Journal of Physiology. 1969, 216: 421-424.PubMedGoogle Scholar
- Taya K, Greenwald GS: In vivo and in vitro ovarian steroidogenesis in the long term hypophysectomized rat. Endocrinology. 1982, 110: 390-397.View ArticlePubMedGoogle Scholar
- Bowen JM, Keyes PL, Warren JS, Townson DH: Prolactin-induced regression of the rat corpus luteum: expression of monocyte chemoattractant protein-1 and invasion of macrophages. Biology of Reproduction. 1996, 54: 1120-1127. (published erratum appears in Biology of Reproduction 1996, 55: 224.View ArticlePubMedGoogle Scholar
- Telleria CM, Parmer TG, Zhong L, Clarke DL, Albarracin CT, Duan WR, Linzer DIH, Gibori G: The different forms of the prolactin receptor in the rat corpus luteum: developmental expression and hormonal regulation in pregnancy. Endocrinology. 1997, 138: 4812-4820.PubMedGoogle Scholar
- Kuranaga E, Kanuka H, Hirabayashi K, Suzuki M, Nishihara M, Takahashi M: Progesterone is a cell death suppressor that downregulates Fas expression in rat corpus luteum. FEBS Letters. 2000, 466: 279-282. 10.1016/S0014-5793(00)01090-5.View ArticlePubMedGoogle Scholar
- Rueda BR, Hendry IR, Hendry WJ, Stormshak F, Slayden OD, Davis JS: Decreased progesterone levels and progesterone receptor antagonists promote apoptotic cell death in bovine luteal cells. Biology of Reproduction. 2000, 62: 269-276.View ArticlePubMedGoogle Scholar
- Telleria CM, Goyeneche AA, Cavicchia JC, Stati AO, Deis RP: Apoptosis induced by antigestagen RU486 in rat corpus luteum of pregnancy. Endocrine. 2001, 15: 147-155.View ArticlePubMedGoogle Scholar
- Goyeneche AA, Deis RP, Gibori G, Telleria CM: Progesterone promotes survival of the rat corpus luteum in the absence of cognate receptors. Biology of Reproduction. 2003, 68: 151-158.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.