Leydig Cell Development

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Leydig cells were first described by the German histologist Franz Leydig in 1850 (1). In all mammalian species, Leydig cells are located in the interstitial compartment of the testis, between and surrounding the seminiferous tubules (2). Human Leydig cells are epithelioid and ovoid or polygonal. Other cytological features include eosinophilic cytoplasm, euchromatic round eccentric nuclei with a peripheral distribution of heterochro-matin, and conspicuous nucleolus. The predominant cytoplasmic organelle is the smooth endoplasmic reticulum (SER), which is characteristically more abundant in steroido-genic cells when compared to other cell types. Mitochondria and lipid droplets are also numerous in Leydig cells and play a role in steroidogenesis that is discussed later in this

From: Male Hypogonadism: Basic, Clinical, and Therapeutic Principles Edited by: S. J. Winters © Humana Press Inc., Totowa, NJ

Male Hypogonadism

Fig. 1. Testicular interstitial space of an adult man (original image magnification X 7,000). This semithin plastic section shows mature Leydig cells surrounding a capillary. In humans, Leydig cells are embedded in a loose connective tissue. The arrows point to Reinke crystals in the cytoplasm of Leydig cells. (Photo supplied by Dr. Hector Chemes, from ref. 13, with the publisher's permission.)

Fig. 1. Testicular interstitial space of an adult man (original image magnification X 7,000). This semithin plastic section shows mature Leydig cells surrounding a capillary. In humans, Leydig cells are embedded in a loose connective tissue. The arrows point to Reinke crystals in the cytoplasm of Leydig cells. (Photo supplied by Dr. Hector Chemes, from ref. 13, with the publisher's permission.)

Reinke Crystals Leydig
Fig. 2. A Reinke crystal. This electron micrograph (original image magnification X 50,000) shows the highly ordered lattice of filaments within these crystals. (Photo supplied by Dr. Hector Chemes, from ref. 13, with permission from the publisher.)

chapter (3,4). Reinke crystals are observed exclusively in human Leydig cells and are believed to be indicative of diminished steroidogenic capacity during aging (5-7). Human Leydig cell structure and Reinke crystals are shown in Figs. 1 and 2.

In humans, blood levels of testosterone peak three times during development (8). The first peak occurs at 12-14 wk of gestation, during the fetal differentiation of Ley-dig cells (9). Testosterone levels then decline and are low for the remainder of gestation and the early neonatal period. A second peak at 2 mo postpartum is associated with renewed Leydig cell proliferation. Leydig cells then atrophy a second time, and, for the next decade, the interstitium is populated by steroidogenically inactive precursor cells. The adult generation of Leydig cells differentiates pubertally and is complete by 12 to 13 yr of age. Serum levels of testosterone average 6 ng/mL during adulthood (10). Finally, there is a decline in testosterone secretion with aging, which varies in its age of onset. The age-related testosterone decrease is caused primarily by gradual atrophy and loss of adult Leydig cells and also by declines in steroidogenic capacity (11). The fetal, neonatal, and adult epochs of testosterone secretion are associated with three separate waves of increases and declines in Leydig cell numbers (12).

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