Female mammals reproduce in cycles. In women and some other primates the cycle is named after its most visible event, menstruation; in most other mammals it is called the oestrous cycle, after the period of sexual receptivity around ovulation. In both cases the cycle is driven by a conversation between the brain, the pituitary gland, the ovary and the uterus, carried by hormones. At the heart of the second half of the cycle lies a short-lived endocrine gland, the corpus luteum, whose main product is the steroid hormone progesterone.
The human cycle in outline
According to the NHS, a menstrual cycle usually lasts about 28 days, but anything from 21 to 35 days is common, and bleeding lasts between two and seven days. Ovulation takes place about 12 to 16 days before the next period. Periods usually start around the age of 12 and continue until the menopause, which in the UK occurs at an average age of 51.
The first half of the cycle, the follicular phase, is dominated by the growing follicle and its oestrogen output; the mechanisms are described on the ovarian follicles and ovulation page. After ovulation, the luteal phase is dominated by progesterone from the corpus luteum, which prepares the uterine lining for a possible pregnancy. If no embryo implants, the corpus luteum regresses, progesterone falls, and this withdrawal of progesterone is the trigger for menstruation.
The corpus luteum: a gland built to disappear
The corpus luteum (Latin for “yellow body”) develops from the cells left behind in the follicle after ovulation. Luteinising hormone (LH) from the pituitary is important for its development and function in most mammals, although growth hormone, prolactin and oestradiol also play a role in some species. The mature gland contains at least two kinds of hormone-producing cell:
- small luteal cells, derived from the theca cells of the follicle, which respond to LH by increasing progesterone output;
- large luteal cells, derived from granulosa cells, which carry receptors for prostaglandin F2α and, in cattle, produce many times more progesterone than small cells.
Progesterone is made from cholesterol, taken up mainly from blood lipoproteins. A transport protein, StAR, moves cholesterol into the mitochondria, where it is converted to pregnenolone, the rate-limiting step, and then to progesterone. To supply this activity, the corpus luteum develops one of the richest blood supplies, per unit of tissue, of any organ; almost every steroid-producing cell touches a capillary, and endothelial cells make up roughly half of the cells in the mature gland. Its importance is clear in human pregnancy: removal of the corpus luteum in the first trimester leads to miscarriage.
Luteolysis: how the cycle resets
If pregnancy does not occur, the corpus luteum must regress so that a new follicle can grow and ovulate. This process, luteolysis, has two parts: a functional phase, in which progesterone output falls, and a structural phase, in which the gland is dismantled and replaced by a small scar, the corpus albicans.
In sheep, cattle and many other non-primate species, the trigger is a series of pulses of prostaglandin F2α released by the uterus. The early corpus luteum is resistant to this signal and becomes sensitive only later in the luteal phase. In primates the role of prostaglandin F2α remains controversial; if it acts at all, it appears to be produced within the ovary rather than by the uterus, and a decline in gonadotrophin support is thought to be important. The structural phase involves an influx of immune cells such as macrophages, the release of inflammatory cytokines and the breakdown of the dense capillary network. Reviews stress that the exact mechanism of this vascular regression is still unknown.
Rescue in pregnancy: maternal recognition
If an embryo is present, it must signal its existence in time to stop luteolysis, because continued progesterone secretion is required to maintain pregnancy. Mammals have evolved strikingly different solutions to this problem, known as the maternal recognition of pregnancy:
- in primates and horses, the embryo secretes a chorionic gonadotrophin, a hormone that acts through the same receptor as LH to keep the corpus luteum alive;
- in domestic ruminants, the elongating embryo secretes an anti-luteolytic signal, interferon tau, which suppresses the uterine release of prostaglandin F2α by reducing oestrogen and oxytocin receptors in the uterine lining;
- in most rodents, mating itself sets off a neuroendocrine reflex that changes pituitary hormone secretion, including surges of prolactin, to sustain the corpus luteum.
The ruminant story illustrates how the field developed. The protein was first described in 1982 as “ovine trophoblast protein-1”, recognised as an interferon in 1987 and later renamed interferon tau. In sheep its anti-luteolytic activity is detectable in embryos around days 14 to 16 of pregnancy, and in cattle production rises as the embryo elongates from about day 12 or 13.
Established and still debated
The essentials of the cycle are well established: progesterone from the corpus luteum prepares and sustains the uterus, its withdrawal triggers menstruation in women, uterine prostaglandin F2α ends the luteal phase in ruminants, and embryos rescue the corpus luteum by species-specific signals. Active areas of research include the cellular events of luteal regression, the role of blood vessels and immune cells in building and dismantling the gland, the trigger for luteolysis in primates, and how the corpus luteum’s life span is tuned in different species. The papers collected in this archive, from studies of luteal cell composition and angiogenesis in cattle to work on plant-derived oestrogens and steroid receptors, reflect how broad the questions about sex steroids remain.
Sources
- NHS, “Periods” (health A–Z)
- Niswender GD et al., Physiological Reviews, 2000 — Mechanisms controlling the function and life span of the corpus luteum (doi:10.1152/physrev.2000.80.1.1)
- Przygrodzka E, Plewes MR, Davis JS, International Journal of Molecular Sciences, 2021 — Luteinizing hormone regulation of inter-organelle communication and fate of the corpus luteum (doi:10.3390/ijms22189972)
- Monaco CF, Davis JS, Frontiers in Physiology, 2023 — Mechanisms of angioregression of the corpus luteum (doi:10.3389/fphys.2023.1254943)
- Bai H et al., Journal of Reproduction and Development, 2022 — Recent progress of interferon-tau research and potential direction beyond pregnancy recognition (doi:10.1262/jrd.2022-061)
- Critchley HOD et al., Physiological Reviews, 2020 — Physiology of the endometrium and regulation of menstruation (doi:10.1152/physrev.00031.2019)
References from the journal archive
These articles were published in Reproduction, the Journal of Reproduction and Fertility or Reviews of Reproduction and are still cited at their old addresses on this domain. Each link leads to the publisher’s version through its DOI.
- SEX STEROID HORMONES AND VOLUNTARY EXERCISE IN RATS
- THE REPRODUCTIVE CYCLE OF THE MALE INDIAN PALM SQUIRREL, FUNAMBULUS PENNANTI WROUGHTON
- REPRODUCTIVE CYCLE OF THE FEMALE FIVE-STRIPED INDIAN PALM SQUIRREL, FUNAMBULUS PENNANTI (WROUGHTON)
- EFFECT OF RAMS ON THE DURATION OF OESTROUS BEHAVIOUR IN EWES
- THE REPRODUCTIVE CYCLE OF THE FEMALE RED DEER, CERVUS ELAPHUS L.
- EFFECT OF SHORT-TERM PROGESTERONE TREATMENT ON OESTROUS RESPONSE AND FERTILITY IN HEIFERS
- Abortifacient effect of steroids from Ananas comosus and their analogues on mice
- Seasonal variations in post-partum plasma progesterone levels and conception in primiparous and multiparous dairy cows
- Milk progesterone levels in relation to conception, repeat breeding and factors influencing acyclicity in dairy cows
- In-vitro contractility of rat seminiferous tubules in response to prostaglandins, cyclic GMP, testosterone and 2,4′-dibromoacetophenone
- The role of protein synthesis in regulation of oestradiol-17β in the pro-oestrous hamster
- Improvement of sheep fecundity by treatment with antisera to gonadal steroids
- Oviposition and the plasma concentrations of LH, progesterone and corticosterone in bobwhite quail ( Colinus virginianus ) fed parathion
- Effect of exogenous oestradiol-17β on gonadotrophin secretion in post-partum beef cows
- Effect of betamethasone treatment on luteal lifespan and the LH response to GnRH in dairy cows
- Angiogenic activity of bovine corpora lutea at several stages of luteal development
- Changes in LH pulse frequency and serum progesterone concentrations during the transition to breeding season in ewes
- Plasma concentrations of progesterone, oestrogens, testosterone and LH-like activity during the oestrous cycle of the camel ( Camelus dromedarius )
- Relationship between blood flow and steroidogenesis in the rabbit corpus luteum
- Cellular composition of the cyclic corpus luteum of the cow
- Effects of naloxone on the oestradiol-induced LH surge and cortisol release in transported cows
- Luteal inadequacy during the early luteal phase of subfertile cows
- Reproductive cycle of the steppe polecat ( Mustela eversmanni )
- Effects of progestagen treatment on concentrations of prostaglandins and oxytocin in plasma from the posterior vena cava of post-partum beef cows
- Reproductive activity in captive female cheetahs ( Acinonyx jubatus ) assessed by faecal steroids
- Ultrasound image attributes of the bovine corpus luteum: structural and functional correlates
- Steroid control of monoamines in relation to sexual behaviour
- Distribution of extracellular matrix components in the developing ruminant corpus luteum: a wound repair hypothesis for luteinization
- Inter-relationships between endothelin and prostaglandin F2alpha in corpus luteum function
- Role of progesterone in peripheral nerve repair
- Function and localization of oxytocin receptors in the reproductive tissue of rams
- Inter-relationships among gonadotrophins, reproductive steroids and inhibin in freemartin ewes
- Neural signals that regulate GnRH neurones directly during the oestrous cycle
- Effect of ram introduction on the oestrous cycle of springbok ewes (Antidorcas marsupialis)
- Molecular control of luteal secretion of progesterone
- Non-invasive assessment of oestrous cycles and evaluation of reproductive seasonality in the female wild black rhinoceros (Diceros bicornis minor)
- Oestrogenic activity of the hop phyto-oestrogen, 8-prenylnaringenin
- Reproductive tissue selective actions of progesterone receptors
- Adult-only exposure of male rats to a diet of high phytoestrogen content increases apoptosis of meiotic and post-meiotic germ cells
- A novel physiological culture system that mimics luteal angiogenesis
- Expression and regulation of oestrogen receptors in the human corpus luteum
- The role of glia in the hypothalamus: implications for gonadal steroid feedback and reproductive neuroendocrine output
- Effect of DHEA and metformin on corpus luteum in mice
- FGF2 is crucial for the development of bovine luteal endothelial networks in vitro
- Excretion and binding of tritium-labelled oestradiol in mice ( Mus musculus ): implications for the Bruce effect
- Polyunsaturated fatty acids modulate prostaglandin synthesis by ovine amnion cells in vitro
- Unique biphasic progestagen profile in parturient and non-parturient giant pandas ( Ailuropoda melanoleuca ) as determined by faecal hormone monitoring
- Escherichia coli lipopolysaccharide administration transiently suppresses luteal structure and function in diestrous cows
- Fibroblast growth factor 2 is a key determinant of vascular sprouting during bovine luteal angiogenesis
- Reproductive consequences of developmental phytoestrogen exposure
- Role of the cell cycle in regression of the corpus luteum
- Free and sulfated steroids secretion in postpubertal boars ( Sus scrofa domestica )
- Short oestrous cycles in sheep during anoestrus involve defects in progesterone biosynthesis and luteal neovascularisation
- Antiprogestins in gynecological diseases
- Notch signaling represses GATA4-induced expression of genes involved in steroid biosynthesis
- LPS-mediated effects and spatio-temporal expression of TLR2 and TLR4 in the bovine corpus luteum
- Steroid hormones, prostanoids, and angiogenic systems during rescue of the corpus luteum in pigs