L. Hagenäs

Sertoli cell origin of testicular androgen-binding protein (ABP)

In this report it is suggested that the specific adrogen-binding protein (ABP), previously shown to originate in the testis of rat and other species, is produced by the Sertoli cells. This suggestion is based upon the following experimental findings: 1) ABP was found in high concentrations in testicular efferent duct fluid but only in trace amounts in inter-tubular lymph. i) ABP could be recovered from crude preparations of testis tubules, but not from Leydig cells from the same testes. 3) Testes whose germinal epithelium had been severly damaged by gamma irradiation showed no decrease in ABP content. The transport of ABP to epididymis was also preserved as judged from the levels of ABP in caput epididymis. 4) Testes that were completely devoid of germ cells following prenatal gamma irradiation showed high levels of ABP, These high levels approached zero following hypophysectomy, but could be restored by FSH administration to the hypophysectomized animals. ABP has been well characterized and now provides a valuable experimental tool as an indicator of Sertoli cell function.

BLOOD-TESTIS BARRIER: Maintained Function of Inter-Sertoli Cell Junctions in Experimental Cryptorchidism in the Rat, as Judged by a Simple Lanthanum-Immersion Technique

In order to elucidate the mechanisms behind the deleterious effects on the germinal epithelium of experimental cryptorchidism the hypothesis that a leaking blood‐testis barrier is the cause of the damage was tested. The permeability of the specialized inter‐ Sertoli cell junctions to lanthanum after experimental cryptorchidism for 0.5 to 12 days was studied in the rat. In none of the time periods studied lanthanum had penetrated beyond the inter‐Sertoli cell junctions. A simple lanthanum immersion technique was used. Testes of 15‐days old rats (before the development of the barrier) were used as a positive control of the method, and in these testes lanthanum had penetrated up to the future lumen.

Testicular Androgen Binding Protein (ABP) — A Parameter of Sertoli Cell Secretory Function

Using ABP as an index of Sertoli cell secretory function, several important features of the Sertoli cell have emerged: 1. The stimulation of ABP production by FSH clearly points to the Sertoli cell as a target cell for FSH (3,4,9-16,21,24). 2. The dramatic effects of androgens on ABP production both in immature and mature rats also suggest that the Sertoli cell is a target cell for androgen (3,12,14,16,25). 3. The striking reduction in ABP production in the cryptorchid testis raises the question whether impairment of Sertoli cell function is the primary reason for the loss of germ cells that occurs in this condition (20). 4. Drugs like nitrofurazone or ethionine, or X-irradiation only slightly affect the secretory function of the Sertoli cells (ABP production), indicating that these treatments most probably have direct effects on the germ cells as well. Thus, measurement of ABP production rate is a very important tool in order to evaluate how hormones, drugs and physical injuries might affect the secretory function of the Sertoli cell. This test system might be of great use in order to study the physiology and hormonal regulation of the Sertoli cells. It might also be valuable in pharmacological and toxicological studies.

Co-Occurring SHOC2 and PTPN11 Mutations in a Patient With Severe/Complex Noonan Syndrome-Like Phenotype

Noonan syndrome (NS) is a heterogeneous disorder caused by activating mutations in the RAS‐MAPK signaling pathway. It is associated with variable clinical expression including short stature, congenital heart defect, unusual pectus deformity, and typical facial features and the inheritance is autosomal dominant. Here, we present a clinical and molecular characterization of a patient with Noonan‐like syndrome with loose anagen hair phenotype and additional features including mild psychomotor developmental delay, osteoporosis, gingival hyperplasia, spinal neuroblastoma, intrathoracic extramedullary hematopoiesis, and liver hemangioma. Mutation analysis of PTPN11, SOS1, RAF1, KRAS, BRAF, MEK1, MEK2, NRAS, and SHOC2 was conducted, revealing a co‐occurrence of two heterozygous previously identified mutations in the index patient. The mutation SHOC2 c.4Au2009>u2009G; p.Ser2Gly represents a de novo mutation, whereas, PTPN11 c.1226Gu2009>u2009C; p.Gly409Ala was inherited from the mother and also identified in the brother. The mother and the brother present with some NS manifestations, such as short stature, delayed puberty, keratosis pilaris, café‐au‐lait spots, refraction error (mother), and undescended testis (brother), but no NS facial features, supporting the notion that the PTPN11 p.Gly409Ala mutation leads to a relatively mild phenotype. We propose that, the atypical phenotype of the young woman with NS reported here is an additive effect, where the PTPN11 mutation acts as a modifier. Interestingly, co‐occurrence of RAS‐MAPK mutations has been previously identified in a few patients with variable NS or neurofibromatosis‐NS phenotypes. Taken together, the results suggest that co‐occurrence of mutations or modifying loci in the RAS‐MAPK pathway may contribute to the clinical variability observed among NS patients.

Growth dependence on insulin-like growth factor-1 during the ketogenic diet.

Purpose:u2002 To examine the influence of the ketogenic diet (KD) on linear growth and insulin‐like growth factor I (IGF‐I) levels in children with pharmacotherapy‐resistant epilepsy.

Growth charts for monitoring postnatal growth at NICU of extreme preterm‐born infants

Aim:u2002 To provide growth charts for clinical monitoring of extra‐uterine growth from birth to full‐term age, in infants born before 26u2003weeks of gestation, hospitalized at neonatal intensive care unit (NICU), and compare it to the commonly used Swedish preterm birth‐size reference.

In vitro synthesis of rat testicular androgen-binding protein (ABP)

Testicular tissue from immature and adult rats shows in vitro synthesis of androgen-binding protein (ABP). The ABP synthesis is dependent on a complete tissue culture medium, the incubation temperature and the age of the rats. ABP synthesis is inhibited at 0 degrees C or in the presence of cycloheximide, puromycin or sodium fluoride. Immature (17-25-day-old rat) testes showed a higher rate of ABP synthesis per 100 mg tissue than adult rat testes during baseline conditions (no additions to the medium). Addition of NIH-FSH-S10 or testosterone to the medium increases the production of ABP by the testicular minces. The in vitro techniques have proved to be useful for studies of direct hormonal influence on the Sertoli cell protein synthesis.

In Vitro Synthesis of Testicular Androgen Binding Protein (ABP): Stimulation by FSH and Androgen

Androgen binding protein (ABP) was first demonstrated in the rat epididymis (1,2). It was subsequently shown that it originates in the testes, is secreted into the lumen of the seminiferous tubule and transported to the caput epididymidis where it is partially (in the rat) or completely (in the rabbit) degraded (3,4,5). ABP is produced in the Sertoli cells (6–12) and specifically stimulated by FSH (6,7,9,10,13). Being hitherto the only well characterized specific product of the Sertoli cell, it offers itself as an index of the functional activity of the Sertoli cell, as well as a specific end point of FSH action in the testis.

Androgen Binding and Transport in Testis and Epididymis

Publisher Summary This chapter elaborates the different aspects of androgen binding and transport in testin and epididymis. Along with the prostate and the seminal vesicles, the epididymis has long been known to be heavily dependent on androgenic hormones for its normal gross appearance. The testis, however, being the major source of circulating androgenic hormones, escaped detection as a major androgen-responsive tissue. The observations that most androgenic hormones not only stem from the testis, but also exert direct actions on testicular events, were made during studies on the regulation of spermatogenesis. The epididymis is completely dependent on androgenic hormones for its development during fetal life, as well as for its function in the mature male. The nuclear hormone can be extracted as a steroid-protein complex by high ionic strength buffers. The potent antiandrogen cyproterone acetate decreased nuclear uptake of radioactive hormone to the same degree as it inhibited binding to cytoplasmic receptors, also indicating the relationship between cytoplasmic receptors and binding to chromatin.

Growth charts and long‐term sequelae in extreme preterm infants – from full‐term age to 10 years

To describe growth pattern from full‐term age to 10 years in infants born before 26 weeks of gestation.