" Holland in 1500 was a small European nation, but extremely energetic, practical, and progressive, with a strong emphasis on trade. Particularly in the northern provinces, the Dutch embraced Protestant Christianity during the sixteenth century, supplanting Catholicism. They were aggressive and dynamic traders, well-positioned to transport goods to and from the Baltic and North Atlantic, and the interior of Europe up the Rhine River. They built efficient ships that carried large cargoes with small crews. Very limited in land, they developed an intense agriculture and began reclaiming lowlands from the sea.
By accident of marriage and inheritance, control of the now largely Protestant Holland shifted to Catholic Spain in the mid-sixteenth century, and Spanish kings sought, in turn, to supplant Protestantism within their realm. This led to a revolt against Spain. Although at a great disadvantage in overall wealth and power, the Dutch proved a tough opponent and drew allies to their side. By 1609 Holland was virtually independent.
In the era of colonial expansion by great empires, the Dutch pursued business opportunities. They were soon engaged in the trade with the Americas, despite Spanish attempts to exclude non-allies. The efficiency of their ships made them attractive as low-cost carriers. They built a business carrying and processing sugar and other goods out of Portuguese Brazil. When the Spanish allied with Portugal and closed the Portuguese ports to the Dutch, the Dutch seized several islands, including Aruba and Curaçao.
In 1610 Henry Hudson explored the North American coast and rediscovered both the river now named after him and the great harbor of modern-day New York City. After several trading voyages to the area seeking furs, the Dutch planted a small trading outpost up the river near Albany in 1614 and later a more permanent settlement on Manhattan Island. The relatively few colonists were more interested in trade profits than in establishing a lasting and well-defended colony. New Amsterdam fell easily to a British fleet commanded by the Duke of York in 1664. The Dutch regained it briefly in 1673, but ceded it permanently to Britain in 1674.
The Dutch made their biggest mark in the East Indies. Following in the wake of the Portuguese around Africa in the early 1600s, agents of the Dutch East India Company took over much of the East India trade, together with England. "
The pharmacodynamics of anabolic steroids are unlike peptide hormones. Water-soluble peptide hormones cannot penetrate the fatty cell membrane and only indirectly affect the nucleus of target cells through their interaction with the cell’s surface receptors . Conversely, as fat-soluble hormones, anabolic steroids are membrane permeable and influence the nucleus of cells by direct action. The pharmacodynamic action of anabolic steroids begin when the exogenous hormone penetrates the membrane of the target cell and binds to an androgen receptor located in the cytoplasm of that cell. From there, the compound hormone-receptor diffuses into the nucleus, where it either alters the expression of genes [ 20 ] or activates processes that send signals to other parts of the cell. [ 21 ] Different types of anabolic steroids bind to the androgen receptor with different affinities , depending on their chemical structure. [ 3 ] Some anabolic steroids such as methandrostenolone bind weakly to this receptor in vitro, but still exhibit androgenic effects in vivo. The reason for this discrepancy is not known. [ 22 ] On the other hand, steroids such as oxandrolone bind tightly to the receptor and act mostly on gene expression . [ citation needed ]