The first half of this review examines the boundary between endocrinology and embryonic development, with the aim of highlighting the way hormones and signaling systems regulate the complex morphological changes to enable the intra-abdominal fetal testes to reach the scrotum. The genitoinguinal ligament, or gubernaculum, first enlarges to hold the testis near the groin, and then it develops limb-bud-like properties and migrates across the pubic region to reach the scrotum. Recent advances show key roles for insulin-like hormone 3 in the first step, with androgen and the genitofemoral nerve involved in the second step. The mammary line may also be involved in initiating the migration. The key events in early postnatal germ cell development are then reviewed because there is mounting evidence for this to be crucial in preventing infertility and malignancy later in life. We review the recent advances in what is known about the etiology of cryptorchidism and summarize the syndromes where a specific molecular cause has been found. Finally, we cover the recent literature on timing of surgery, the issues around acquired cryptorchidism, and the limited role of hormone therapy. We conclude with some observations about the differences between animal models and baby boys with cryptorchidism.

Binding of radioactive thyroxine to proteins in the plasma of vertebrates was studied by electrophoresis followed by autoradiography. Albumin was found to be a thyroxine carrier in the blood of all studied fish, amphibians, reptiles, monotremes, marsupials, eutherians (placental mammals), and birds. Thyroxine binding to transthyretin was detected in the blood of eutherians, diprotodont marsupials, and birds, but not in blood from fish, toads, reptiles, monotremes, and Australian polyprotodont marsupials. Globulins binding thyroxine were only observed in the plasma of some mammals. Apparently, albumin is the phylogenetically oldest thyroxine carrier in vertebrate blood. Transthyretin gene expression in the liver developed in parallel, and independently, in the evolutionary lineages leading to eutherians, to diprotodont marsupials, and to birds. In contrast, high transthyretin mRNA levels, strong synthesis, and secretion of transthyretin in choroid plexus from reptiles and birds indicate that transthyretin gene expression in the choroid plexus evolved much earlier than in the liver, probably at the stage of the stem reptiles. NH2-terminal sequence analysis suggests a change of transthyretin pre-mRNA splicing during evolution.

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A cell culture model for the blood-cerebrospinal fluid barrier in choroid plexus was developed. The relationship between synthesis and secretion of transthyretin across a layer of epithelial cells derived from rat choroid plexus and the transport of T4 was analyzed in a two-chamber system. Choroid plexus cells were dispersed and placed on a porous filter suspended in cell culture medium. A monolayer of polarized epithelial cells developed after 5 days in culture, separating fluid in the upper (apical) chamber from fluid in the lower (basal) chamber. Electrical resistance across the cell layer was 100 Ohm/cm2. Transthyretin was synthesized and secreted by these cells. Over 32 h, transthyretin accumulated in the fluid in the apical chamber to twice the concentration in the basal chamber. [125I]T4 added to the basal chamber permeated to the apical fluid and accumulated in the apical chamber to twice the concentration in the basal fluid. Upon inhibition of protein synthesis, T4 equilibrated to a similar concentration in the two chambers. Thus, the accumulation of T4 in the apical chamber required continuing protein synthesis. Competitive inhibition of T4 binding to transthyretin by EMD 21388 also prevented the accumulation of T4 to a higher concentration in the upper than in the lower chamber. These data suggest that T4 partitions through the choroid plexus and that transthyretin synthesis and secretion by the choroid plexus determines the concentration of T4 in the apical fluid. A model is proposed for the involvement of transthyretin secreted by the choroid plexus, in the in vivo distribution of T4 in the brain.