Reporter and Curator: Dr. Sudipta Saha, Ph.D.
Leptin is considered to have an important role in reproductive functions, including menstrual-cycle regulation, pregnancy, and lactation. The absence of leptin action caused by functional mutations in the leptin gene (LEP) or the leptin receptor gene (LEPR) has been linked to infertility in rodents and humans. A pregnancy was reported in a woman despite absent leptin signaling.
In 1998, it was reported the case of a morbidly obese patient with a rare homozygous LEPR mutation, which was shared by several affected siblings. The mutation was found in the patient’s blood and adipose tissue, indicating no evidence of chimerism. She had been followed for morbid obesity since early childhood, with abnormal compulsive-feeding behaviors and reduced levels of growth hormone and thyrotropin. She entered puberty late, with irregular cycles after the age of 17 years. Repeated evaluations of sex-hormone levels were considered to be normal after the age of 18 years. The patient underwent abdominoplasty at the age of 16 years and gastric-bypass surgery at the age of 24 years. Six months after gastric bypass, her weight had decreased from 220 kg (485 lb) to 170 kg (375 lb), with a concurrent decrease in the body-mass index (the weight in kilograms divided by the square of the height in meters) from 81 to 62. She was counseled regarding contraception and was prescribed oral contraceptives. Two years after gastric bypass, just before an unplanned pregnancy, she had no diabetes, hypertension, respiratory disorders, or other recognized complications of obesity.
Ultrasonographic examinations during pregnancy were considered normal except for suspected macrosomia in the third trimester. The patient’s total weight gain during pregnancy was 50 kg (110 lb) from a prepregnancy weight of 180 kg (397 lb). Routine screening for gestational diabetes was normal. Although occasional elevated blood sugar levels were documented during the pregnancy, the glycated hemoglobin level in the third trimester was 5.6%. At 37 weeks 5 days of gestation (on the basis of first-trimester ultrasonography), the patient delivered a son by elective cesarean section, which was performed because of breech presentation and suspected macrosomia under epidural anesthesia after the administration of glucocorticoids for fetal lung maturation. The birth weight was 3720 g (8.2 lb), and the length was 50 cm (19.7 in.); the head circumference was 36.5 cm (14.4 in.), which was above the 90th percentile. The patient’s postpartum course was complicated by a wound infection. The infant’s neonatal course was complicated by hypoglycemia, hypocalcemia, and jaundice requiring phototherapy. The patient briefly breast-fed her child. The child’s growth and development have been normal; his weight at 1 year was 14 kg (31 lb).
This case of a natural pregnancy in a woman with a homozygous LEPR mutation calls into question the belief that leptin function is critical to reproductive function.
Source References:
http://www.nejm.org/doi/full/10.1056/NEJMc1200116
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Alan F. Kaul, PharmD., MS, MBA, FCCP
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Demet Sag, Ph.D., CRA, GCP
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Dr. Saha,
Thank you for this post. In will be nice to have another post on Leptin. I’ll research and e-mail resources. During Novemser, let’s have, three post in the Endocrinology Genomics and Reproductive Genomics per material in your hands.
Thank you
Aviva
Let’s have in November, one post on Leptin and three on endocrinology Genomics.
Thank you for this fascinating post
[…] Pregnancy with a Leptin-Receptor Mutation […]
[…] Pregnancy with a Leptin-Receptor Mutation […]
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.